instrumental techniques in drug discovery
Post on 29-May-2018
213 Views
Preview:
TRANSCRIPT
-
8/9/2019 Instrumental techniques in Drug Discovery
1/110
-
8/9/2019 Instrumental techniques in Drug Discovery
2/110
Edx lvth ldwdaiskde|
N svijdzz x`mj` nssamdz |i lvthz! sviltj|z nel
svi|ijiaz |i fd tzdl ie `tkne ztfodj|z%
>%Lvth lmzjiwdv}
6%Svd jamemjna ldwdaiskde|
:%Jamemjna |vmna
-
8/9/2019 Instrumental techniques in Drug Discovery
3/110
Ivhnemj J`dkmz|v} mewiawdl me
Z}e|`dzmz ' Stvmgmjn|mie Ivhnemj j`dkmz|z z}e|`dzmd edx lvth jiksitelz nz xdaa nz
mzian|d nel j`nvnj|dvmd en|tvna sviltj|z! ztj` nz nabnaimlz%
Me dnj` jnzd! xd `nwd |i dwnatn|d |`d jiksadp vdan|miez`msz
fd|xdde j`dkmjna z|vtj|tvd nel s`nvknjiaihmjna nj|mie%
z|vtj|tvd! nel wdv} zknaa j`nehdz kn} svi+gitela} kilmg} |`d
s`nvknjiaihmjna dggdj| ZNV-%
Z|vtj|tvna kilmgmjn|miez?
vdsanjmeh ied hvits xm|` nei|`dv n| n zsdjmgmj sime| me |`d kiadjtad!
z`mg|meh |`d znkd hvits gvik sanjd |i sanjd me |`d snvde| kiadjtad!
zn|tvn|meh wnadejd fielz!
kilmg}meh |`d njmlm|} iv fnzmjm|}%
J`vikn|ihvns`mj |dj`em~tdz `nwd fdde xmlda} tzdl giv |`d
stvmgmjn|mie ig edxa} z}e|`dzmdl jiksitelz% :Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
4/110
Mez|vtkde|na \dj`em~tdz giv
Sviltj| J`nvnj|dvmn|mie \`d gmvz| z|ds me sviltj| j`nvnj|dvmn|mie mz |i
dz|nfamz` |`d svdjmzd j`dkmjna mlde|m|} ig |`d
sviltj|% M| mz mksiv|ne| |i ld|dvkmed x`d|`dv |`d
kn|dvmna mz n jiksitel! m%d% n zmehad j`dkmjna de|m|}!
n kmp|tvd ig jaizda} vdan|dl jiksitelz!
kmp|tvd ig mzikdvz! iv
kdvda} n aiizd kiadjtanv jiksadp ig vdnlma} lmzzijmnfad
jiksiede|z%
Ztj` megivkn|mie mz gtelnkde|na |i n svisdv
dwnatn|mie ig |`d fmiaihmjna svisdv|mdz ig |`dkn|dvmna%
-
8/9/2019 Instrumental techniques in Drug Discovery
5/110
Sviltj| J`nvnj|dvmn|mie
Giv jiksitelz ig z}e|`d|mj ivmhme?
Mlde|m|} mz tztnaa} jadnva} ldgmedl f} |`d
z}e|`d|mj vit|d dksai}dl% Ki dve zsdj|vizjis j |dj e ~tdz?
>@ nel >:J EKV
MV (megvnvdl zsdj|vizjis}- nvd zdezm|mwd |iiaz givztj` stvsizdz%
4Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
6/110
S`}zmjij`dkmjna j`nvnj|dvmn|mie
|dj`em~tdz
San} n knoiv viad me |`d lvth ldwdaiskde|
svijdzz fdjntzd |`d} `das tz |i teldvz|nel
|`d kdj`nemzk ig lvth ldamwdv}% Lmzziat|mie mz |`d gmvz| z|ds me lvth ldamwdv} f}
ziaml ivna liznhd givkz%
ft| |`d ld|dvkmen|mie ig me wm|vi vdadnzd svigmadzsviwmldz am||ad megivkn|mie ie |`d kdj`nemzk ig
|`d vdadnzd ig NSM gvik |`d sviltj| kn|vmp%
7Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
7/110
M| mz vd~tmvdl |i nzzdzz (tzmeh mez|vtkde|na |dj`em~tdz-?
Me|dvena z|vtj|tvd ig |`d liznhd givk
Kmjvi`ikihdedm|}
Kivs`iaih} ig |`d nsm me |`d liznhd givk
mez|vtkde|na |dj`em~tdz tzdl?
Kmjvizjis} nel dedvh}+lmzsdvzmwd p+vn} zsdj|vizjis}
P+vn} sixldv lmggvnj|mie!
\`dvkna nena}zmz!
G\MV kmjvizsdj|vizjis}!
EKV mknhmeh!
Knzz zsdj|vikd|v}! nel
Vnkne zsdj|vizjis}%
\`d jiaadj|mie nel me|dvsvd|n|mie ig |`d vdzta|z if|nmedl gvik
|`dzd |dj`em~tdz jne fd tzdl |i is|mkmd givktan|mie
ldwdaiskde| nel deztvd |`d jiezmz|dej}! ~tnam|}! nel z|nfmam|} ig
ziaml liznhd givkz% 8Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
8/110
Sviltj| stvmgmjn|mie
Sixdvgta zdsnvn|mwd |dj`em~tdz! snv|mjtanva}j`vikn|ihvns`} me naa m|z kne} givkz! sviwmld
zdezm|mwd kd|`ilz%
Am~tml j`vikn|ihvns`}? mz tzdl giv fi|` stvmgmjn|mie
ig kmp|tvdz ig vdan|dl jiksitelz ztj` nz kmp|tvdz
ig mzikdvz%
Jnsmaanv} hnz j`vikn|ihvns`}? \`d zsddl nel `mh`zdsnvn|mwd sixdv knbd m| snv|mjtanva} tzdgta! mg `mh`a}
zsdjmnamdl |dj`em~td giv |`d zdsnvn|mie ig jiksadp
kmp|tvdz ltvmeh |`d vdzdnvj` s`nzd ig lvth
ldwdaiskde|% 0Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
9/110
X`dvd |`d sviltj| jiezmz|z ig kivd |`ne ied mzikdv! |`d mzikdvz
ktz| fd jnsnfad ig zdsnvn|d mlde|mgmjn|mie nel kdnztvdkde| |i
dz|nfamz` kdnez ig deztvmeh fn|j`+|i+fn|j` jiezmz|dej} ig mzikdv
jiksizm|mie%
Giv kiz| is|mjnaa} nj|mwd jiksitelz! n zmksad sianvmkd|vmj
kdnztvdkde| xmaa ztggmjmde|%
Ijjnzmienaa}! `ixdwdv! x`dvd |`d kdnztvdl vi|n|mie mz zknaa!
kdnztvdkde|z ie n kivd zdezm|mwd mez|vtkde| n| i|`dv
|i zdjtvd nld~tn|d jie|via ig |`d sviltj|%
Me dpjds|miena jnzdz! |`d mlde|mgmjn|mie ig is|mjna mzikdvz lmggdvmeh me
iea} ied ig zdwdvna j`mvna jde|dvz kn} jnaa giv |`d tzd ig is|mjna
vi|n|iv} lmzsdvzmie iv jmvjtanv lmj`vimzk |i sviwmld n ldhvdd ig
zdezm|mwm|} |`n| jneei| fd if|nmedl gvik zmksad kdnztvdkde|z ig
is|mjna vi|n|mie%
EKV mz snv|mjtanva} wnatnfad me lmz|mehtmz`meh hdikd|vmjna mzikdvz%
=Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
10/110
Hinaz nel ifodj|mwdz
Jamemjna s`nvknjiaih} nel s`nvknjikd|vmjz
Zngd|}
Nj|mwm|}
Lmggdvde|mn|mie
Ztjjdzzgta GLN ztfkmzzmie
Knvbd| dpsnezmie nel siz| knvbd|meh ztvwdmaanejd
>3Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
11/110
Lvth lmzjiwdv} svijdzz
Zjvddemeh jiezmz|z ig |dz|meh kne} jiksitelz
me nzzn}z vdadwne| |i |`d lmzdnzd me
~tdz|mie@M\
jie|metd |i z`ix svikmzd ng|dv gtv|`dv
fmiaihmjna nel j`dkmjna j`nvnj|dvz%ADNL
>>Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
12/110
\xi fnzmj z|vn|dh} nvd nssamdl
>% Jiksitel jde|dvdl6% \nvhd| jde|dvdl
>% Jiksitel jde|dvdl nssvinj`?
En|tvna sviltj|z? mzian|dl gvik sane|z!
nemknaz nel kmjviivhnemzkz%
dp% Kivs`med! ^tmemed! N|vismed
Nlvdenamed! \`}vipmed
Sdemjmaame
>6Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
13/110
En|tvna amhnelz
Dpnksadz?
Lisnkmed+ Snvbmezie+ A+lisn
Meztame lmnfd|dz dpihdeitz meztame
>:Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
14/110
6% \nvhd| jde|dvdl nssvinj`
Tzd fmij`dkmjna iv kiadjtanv |nvhd|
Nlw ?
s`nvknjiaihmjna nj|mwm|}
>
-
8/9/2019 Instrumental techniques in Drug Discovery
15/110
Z|vtj|tvd fnzdl nssvinj`
Tzd :+L z|vtj|tvd ig |`d |nvhd| if|nmedl|`vith` p+vn} jv}z|naaihvns`} iv EKV%
Nlw ?
+ i|dej
+amkm|dl etkfdv ig lvthz
Lmznlw ?
+z}e|`dzmz
>4Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
16/110
J`dkmjna z}e|`dzmz?
Fnzdl ie ZNV + dp% @mz|nkmed faijbdvz
Fnzdl ie dene|mikdvz + dp% lisn
Vn|miena nssvinj`?
dp% Svi|ie Stks Me`mfm|ivz%
dp% JIP 6 me`mfm|ivz
Jikfmen|ivmna j`dkmz|v}? Fmi|dj`eiaih}?
dp% Hvix|` gnj|ivz! j}|ibmedz%
>7Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
17/110
Adnl is|mkmn|mie
Me |`mz z|nhd x`dvd s`}zmjna! j`dkmjna! fmiaihmjna nel
s`nvknjiaihmjna svisdv|mdz nvd j`nvnj|dvmdl nel vdgmedl xm|`
|`d ta|mkn|d hina ig zdadj|meh n zmehad kiadjtad |i de|dv me|i
jamemjna |dz|meh nel givkna lvth ldwdaiskde|%
Gnmatvd |i ldkiez|vn|d Dggmjnj}
Aix fminwnmanfmam|}
Dp|dezmwd kd|nfiamzk
Aix ziatfmam|}
\ipmj dggdj|z
Jiz| dggdj|mwdedzz me z}e|`dzmz
>8Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
18/110
Lvth lmzjiwdv}
Mlde|mgmdz me|dvdz|meh lvth jiksitelz! lvth|nvhd|z nel ldamwdv} kdj`nemzkz xm|` |`d
si|de|mna giv ldwdaiskde| me|i sviltj|z%
J`nvnj|dvmd jiksitelz nel |`dmv |nvhd|z Nvd sviig ig jiejds| me en|tvd
Sviwmld gtelnkde|na megivkn|mie ie |nvhd|
fmiaihmjna z}z|dk Mlde|mg} adnl jiksitelz giv gtv|`dv
ldwdaiskde|
>0Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
19/110
Svd jamemjna lvth ldwdaiskde|
Zsnjd |`d hns fd|xdde lvth lmzjiwdv} neljamemjna |vmnaz%
Sviwmld ln|n ie |`d zngd|} nel dggmjnj} ig |`dsviltj|
! !givktan|mie nel snjbnhmeh! Me wmwi z|tlmdz
>=Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
20/110
Me wm|vi z|tl}
Me|nj| jdaa amedz
nzzdzz lvth dggdj|z ie jdaaz xm|` zsdjmgmj LEN
kt|n|mie d vdd z}z|dk
nzzn} ig de}kd nj|mwm|}! vdjds|iv fmelmeh!
svi|dme me|dvnj|mie xm|` zmhena |vnezltj|mie
63Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
21/110
Lvth knetgnj|tvmeh nel givktan|mie
Jieltj|dl teldv jtvvde| hiilknetgnj|tvmeh svnj|mjdz JHKS- htmldamedz
ME+WMWI Z\TLMDZ
SB z|tl} NLKD z|tl} SL z|tl}
\`dvnsdt|mj meldp
\ipmjiaihmjna z|tl}
6>Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
22/110
\ipmjiaihmjna z|tl}
Ifodj|mwdz ?
Njt|d z|tl}
Kd|`il
Nmk ? |i sviwmld zngd|})|`dvnsdt|mj meldp
Ifzdvwn|mie
66Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
23/110
Ztf njt|d z|tl}
nmk ?
\i mlde|mg} |`d |nvhd| ivhne \i ld|dvkmed |`d jamemjna snvnkd|dvz
\i dz|mkn|d |`d zngd|} knvhme
Kd|`il? ?
J`viemj z|tl}Zmkmanv |i ztf njt|d z|tl} dpjds| giv |`d
ltvn|mie
6:Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
24/110
Zsdjmna z|tl}
Dggdj| ie vdsviltj|mwd z}z|dk nel
\dvn|ihdemjm|}
Kt|nhdemjm|}+ nkdz |dz|
Jnvjmeihdemjm|}
6
-
8/9/2019 Instrumental techniques in Drug Discovery
25/110
Jamemjna lvth dwnatn|mie
Nt|`ivmn|mie
Mewdz|mhn|miena edx lvth MEL- ztfkmzzmie
+|`d vn|mienad giv |`d lvth nel sn|mde| hvits
|i fd |vdn|dl
+
+ld|nmadl sane giv jamemjna ldwdaiskde|
+JMF jamemjna mewdz|mhn|ivz fvij`tvd-
Ztfkm||dl |i GLN giv vdwmdx nel sdvkmzzmie |i
svijddl%
64Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
26/110
Lidz m|
xivb me
litfad
Mz m| zngd9 Lidz m| xivb9famel
|vmnaz9
67Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
27/110
NSSVIWNA
Iejd naa jamemjna ln|n `nz fdde ztfkm||dl!
vdwmdxdl nel nssviwna mz hvne|dl |i amjdezd
me knvbd|
Siz| knvbd|me ztvwdmaanejd
Nssviwna |nbdz 7 kie|`z |i 6 }dnvz
68Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
28/110
Nena}|mjna J`dkmz|v}
Ldgmem|mie?
\`d Zjmdejd ' nv| ig ld|dvkmemeh
jiksizm|mie ig kn|dvmna me |dvkz ig dadkde|
Jiejdvedl xm|` J`dkmjna J`nvnj|dvmn|mie ig
kn|dv
Mewiawdz ^tnam|n|mwd nel ^tne|m|n|mwd
ld|dvkmen|mie
60Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
29/110
Hina ig Nena}|mjna kd|`ilz
Nena}zmz^tnam|n|mwdnena}zmz
^tne|m|n|mwdnena}zmz
f} x`mj` |`d nena}|d iv nena}|dz me n znksad nvd
mlde|mgmdl%
^tne|m|n|mwd nena}zmz? N |}sd ig j`dkmjna nena}zmz
f} x`mj` |`d nkite| ig dnj` nena}|d iv nena}|dz me
n znksad mz ld|dvkmedl%
6=Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
30/110
Janzzmgmjn|mie ig Nena}|mjna Kd|`ilz
Nena}|mjna
\dj`em~tdz
J`dkmjna kd|`ilz(Janzzmjna kd|`ilz-
S`}zmjna kd|`ilz(Mez|vtkde|na kd|`ilz-
:3Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
31/110
J`dkmjna Kd|`il (Janzzmjna Kd|`il-
Hvnwmkd|vmj Kd|`il
Wiatkd|vmj Kd|`il
Njml Fnzd |m|vn|miez Edt|vnamn|mie kd|`il- Ip n| ie vd tj| ie | |vn| iez Vd ip kd| i
Svdjmsm|n|mie |m|vn|miez
Jiksadpikd|vmj |m|vn|miez
:>Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
32/110
Janzzmjna Kd|`ilz ig Nena}zmz
Dnva} }dnvz ig j`dkmz|v}
Zdsnvn|mie ig nena}|dz f} svdjmsm|n|mie!dp|vnj|mie! iv lmz|maan|mie%
vdnhde|z |`n| }mdaldl sviltj|z |`n| jital fdvdjihemdl f} |`dmv jiaivz! fimameh iv kda|mehsime|z! ziatfmam|mdz! is|mjna nj|mwm|mdz! iv vdgvnj|mwdmeldpdz%
^tne|m|n|mwd nena}zmz f} hvnwmkd|vmj iv f}|m|vmkd|vmj |dj`em~tdz%
:6Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
33/110
Mez|vtkde|na (S`}zmjna- Kd|`ilz
Mez|vtkde|na
Kd|`ilz
Is|mjna
kd|`ilz
Dadj|vij`dkmjna
kd|`ilz
Kmzjdaaneditz
kd|`ilz
::Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
34/110
Mez|vtkde|na Kd|`ilz
Kdnztvdkde| ig s`}zmjna svisdv|mdz ig nena}|dz + ztj`nz jieltj|mwm|}! dadj|vild si|de|mna! amh`| nfzivs|mie ivdkmzzmie! knzz+|i+j`nvhd vn|mi! nel gativdzjdejd+fdhne |i fd dksai}dl giv ~tne|m|n|mwd nena}zmz igmeiv nemj iv nemj nel fmij`dkmjna nena |dz
Dggmjmde| j`vikn|ihvns`mj zdsnvn|mie |dj`em~tdz nvdtzdl giv |`d zdsnvn|mie ig jiksiede|z ig jiksadpkmp|tvdz%
Mez|vtkde|na Kd|`ilz ig nena}zmz jiaadj|mwd enkd givedxdv kd|`ilz giv zdsnvn|mie nel ld|dvkmen|mie igj`dkmjna zsdjmdz%-
:
-
8/9/2019 Instrumental techniques in Drug Discovery
35/110
Is|mjna Kd|`ilz
Is|mjna kd|`ilz
(Me|dvnj|mie ig DKV-
Nfzivs|mie Dkmzzmiez Zjn||dvmeh Vi|n|mie igig DKV ig DKV
ig DKV DKV
TW+Wmzmfad
MVEKV
P+Vn}
Zsdj|vizjis}
GativizjdejdS`izs`ivdzjdejd
Gankd S`i|ikd|v}
Eds`aikd|v}
\tvfmlikd|v}Vnkne Zsdj|vizjis}
Vdgvnj|vikd|v}
Sianvmkd|v}
:4Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
36/110
Dadj|vi J`dkmjna Kd|`ilz
s@ kd|v} ' Si|de|mikd|v}
Jieltj|ikd|v}
Wia|nkd|v} Sianvihvns`}
Nksdvikd|dv}
Jitaikd|v}
:7Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
37/110
Kmzjdaaneditz kd|`ilz
\`dvkikd|vmj Nena}zmz?
LZJ
\`dvki Hvnwmkd|vmj Nena}zmz
:8Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
38/110
Janzzmgmjn|mie ig Nena}|mjna Kd|`ilz
>% Janzzmjna kd|`ilz
^tnam|n|mwd mlde|mgmjn|mie f} jiaiv!
Fnzdl ie hina ig nssamjn|mie?
melmjn|ivz! fimameh iv kda|meh sime|z! ilivz
^tne|m|n|mwd knzz iv wiatkd (d%h%hvnwmkd|vmj! wiatkd|vmj-
:0Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
39/110
6% Mez|vtkde|na kd|`ilz
^tnam|n|mwd j`vikn|ihvns`}! dadj|vis`ivdzmznel mlde|mgmjn|mie f} kdnztvmeh s`}zmjna
svisdv|} (d%h% zsdj|vizjis}! dadj|vild si|de|mna-
tne|m|n|mwd kdnztvme vi dv| nel
ld|dvkmemeh vdan|miez`ms |i jiejde|vn|mie (d%h%
zsdj|vis`i|ikd|v}! knzz zsdj|vikd|v}-
Ig|de! znkd mez|vtkde|na kd|`il tzdl giv
^tnam|n|mwd nel^tne|m|n|mwd nena}zmz%
:=Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
40/110
\}sdz ig Mez|vtkde|na Kd|`ilz
Zmhena Dpnksad Kd|`il
Vnlmn|mie dkmzzmie Dkmzzmie zsdj|vizjis}
P+vn}! TW! wmzmfad-!
gativdzjdejd!s izs ivdzjdejd!
atkmedzjdejd
Vnlmn|mie nfzivs|mie Nfzivs|mie zsdj|vizjis}zsdj|vis`i|ikd|v}!
s`i|ikd|v}! EKV
dadj|vie zsme vdzienejd
-
8/9/2019 Instrumental techniques in Drug Discovery
41/110
Zmhena Dpnksad Kd|`il
Vnlmn|mie Zjn||dvmeh Vnkne zsdj|vizjis}
Vnlmn|mie vdgvnj|mie Vdgvnj|ikd|v}
n n| ie vnj| ie +vn} ne
Dadj|vie lmggvnj|mie kd|`il
Vnlmn|mie vi|n|mie Sianvmkd|v}
Dadj|vmjna si|de|mna Si|de|mikd|v}
Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
42/110
Zmhena Dpnksad Kd|`il
Dadj|vmjna j`nvhd Jitaikd|v}
Dadj|vmjna jtvvde| Wia|nkkd|v}nksdvikd|v}
sianvihvns`}
Knzz Hvnwmkd|v}
Knzz+|i+j`nvhd vn|mi Knzz zsdj|vikd|v}
Vn|d ig vdnj|mie Gaix meodj|mie nena}zmz
-
8/9/2019 Instrumental techniques in Drug Discovery
43/110
J`nvnj|dvmz|mj
svisdv|}
Mez|vtkde|na Kd|`ilz
Dkmzzmie ig vnlmn|mie Dkmzzmie zsdj|vizjis} (P+vn}! TW! wmzmfad! dadj|vie-2
gativdzjdejd! s`izs`ivdzjdejd! nel atkmedzjdejd (P+vn}! TW!
nel wmzmfad-
Nfzivs|mie ig vnlmn|mie Zsdj|vis`i|ikd|v} nel s`i|ikd|v} (P+vn}! TW! wmzmfad! MV-2
s`i|injitz|mj zsdj|vizjis}2 etjadnv knhed|mj vdzienejd nel
dadj|vie zsme vdzienejd zsdj|vizjis}
Zjn||dvmeh ig vnlmn|mie \tvfmlmkd|v}2 eds`daikd|v}2 Vnkne zsdj|vizjis}
J`dkmjna nel s`}zmjna svisdv|mdz dksai}dl me mez|vtkde|na kd|`ilz?
Lmggvnj|mie ig vnlmn|mie P+Vn} nel dadj|vie lmggvnj|mie kd|`ilz
Vi|n|mie ig vnlmn|mie Sianvmkd|v}2 is|mjna vi|nv} lmzsdvzmie2 jmvjtanv lmj`vimzk
Dadj|vmjna si|de|mna Si|de|mikd|v}2 j`vieisi|de|mikd|v}
Dadj|vmjna j`nvhd Jitaikd|v}
Dadj|vmjna jtvvde| Sianvihvns`}2 nksdvikd|v}
Dadj|vmjna vdzmz|nejd Jieltj|ikd|v}
Knzz+|i+j`nvhd vn|mi Knzz zsdj|vikd|v}
Vn|d ig vdnj|mie Bmed|mj kd|`ilz
\`dvkna svisdv|mdz \`dvkna jieltj|mwm|} nel de|`nas}
Vnlminj|mwm|} Nj|mwn|mie nel mzi|isd lmat|mie kd|`ilz
-
8/9/2019 Instrumental techniques in Drug Discovery
44/110
Mez|vtkde|z giv Nena}zmz
Ln|nDedvh}
z|mktatz
Nena}|dz
(me kn|vmp-
Nena}|mjna
vdzsiezd
Dejildl
megivkn|mie
Mez|vtkde|? zsdj|vis`i|ikd|dv
Z|mktatz? kieij`vikn|mj amh`| dedvh}
Nena}|mjna vdzsiezd? s`i|ijdaa
Ln|n? dadj|vmjna jtvvde|
Ln|n svijdzziv? jtvvde| kd|dv
Vdnlit|? kd|dv zjnad
-
8/9/2019 Instrumental techniques in Drug Discovery
45/110
Dejildl megivkn|mie?
ld|dj|iv ? ldwmjd |`n| melmjn|dz j`nehdz me dewmviekde|
|vnezltjdv ? ldwmjd |`n| jiewdv|z eie+dadj|vmjna |idadj|vmjna ln|n
Eie+dadj|vmjna liknmez Dadj|vmjna liknmez
S`}zmjna Jtvvde|
(amh`| me|dezm|}! jiaitv-
J`dkmjna (s@- Wia|nhd
-
8/9/2019 Instrumental techniques in Drug Discovery
46/110
Nlwne|nhdz ig Mez|vtkde|na Kd|`ilz
@mh` Zdezm|mwm|}
Njjtvnj}
Zknaa Znksad jne fd tzdl Kdnztvdkde|z if|nmedl nvd vdamnfad '
Vdsviltjmfad
Gnz| Ld|dvkmen|mie Jiksadp znksad jne fd `neladl dnzma} Svijdzz
jne fd knld nt|ikn|mj
-
8/9/2019 Instrumental techniques in Drug Discovery
47/110
Amkm|n|miez ig Mez|vtkde|na kd|`ilz
@mh` Jiz|
Edjdzznv} |i tzd vdgdvdejd ztfz|nejd
Zbmaadl Sdvziez nvd vd~tmvdl
-
8/9/2019 Instrumental techniques in Drug Discovery
48/110
-
8/9/2019 Instrumental techniques in Drug Discovery
49/110
MV Zsdj|vizjis}
-
8/9/2019 Instrumental techniques in Drug Discovery
50/110
MEGVNVDL VDHMIE
|i 733 jk+>
MV zsdj|vtk?
Sai| ig\vnzkm||nejd)Nfzivfnejd WZ Gvd~tdej} ig
ZNKSAD
MV \VNEZKM\\DL
NFZIVFDL
43Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
51/110
Kiadjtanv wmfvn|mie
N|ikz oimedl f} jiwnade| fielz teldvhijie|metna wmfvn|miez vdan|mwd |i dnj` i|`dv
\`d dedvhmdz nzzijmn|dl xm|` |`dzd wmfvn|miez
nvd tne|m|mdl% Xm|`me n kiadjtad ieazsdjmgmj wmfvn|miena dedvh} adwdaz nvd naaixdl%
\`d dedvhmdz nzzijmn|dl xm|` |vnezm|miez
fd|xdde wmfvn|miena dedvh} adwdaz giv kiz|jiwnade| fielz nvd gvik 6 |i >3 bjna)kia 0%3+7
6%4 k- |i 6%4 p >3+4 64 k-
Nfzivs|mie ig MV vnlmn|mie me |`mz vdhmie jntzdz
dedvh} adwda |i n `mh`dv ied
MV ZSDJ\VTK VDSVDZDE\Z J@NEHDZ ME
DEDVH] FVITH@\ F] \VNEZM\MIE IGKIADJTADZ GVIK IED WMFVN\MIENA IV
VI\N\MIENA DEDVH] Z\N\D \I NEI\@DV%
46Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
53/110
MV jntzdz n wmfvn|mie iea} mg |`dvd mz n j`nehd
me lmsiad ltvmeh wmfvn|mie
\`dvdgivd z}kkd|vmj fielz nvd menj|mwd%
: + : x ei i zdvwd z vd j iv + ie
ig d|`ned
4:Naamnejd
M g l (MV- l V Z m
-
8/9/2019 Instrumental techniques in Drug Discovery
54/110
Megvnvdl (MV- nel Vnkne Zsdj|vizjismdz
Megvnvdl MV- nel Vnkne zsdj|vizjismdz `nwd fdde z|nelnvl
kd|`ilz ig nena}|mjna s`nvknj} nel j`dkmz|v} giv n aieh|mkd% MV nel Vnkne zsdj|vn! x`mj` nvd jiksadkde|nv} |i
dnj` i|`dv! sviwmld mknhdz ig wmfvn|miez ig |`d n|ikz ig n
jiksitel% \`dvdgivd! fi|` |dj`em~tdz nvd nazi vdgdvvdl |i nz
wmfvn|miena zsdj|vizjis}%
znksad nel ld|dvkmemeh x`n| gvnj|mie ig |`d mejmlde| vnlmn|mie mz
nfzivfdl n| snv|mjtanv gvd~tdej}%
Ie |`d i|`dv `nel! n Vnkne zsdj|vtk mz if|nmedl f} gijtzmeh
kieij`vikn|mj vnlmn|mie ie n znksad nel nena}meh |`d zjn||dvdl
amh`| nz n gtej|mie ig gvd~tdej}%
MV zsdj|vizjis} mz fnzdl ie |`d nfzivs|mie ig
dadj|viknhed|mj vnlmn|mie f} n kiadjtanv z}z|dk!
Vnkne zsdj|vizjis} vdamdz tsie medanz|mj zjn||dvmeh ig
dadj|viknhed|mj vnlmn|mie f} n kiadjtanv z}z|dk% 4
-
8/9/2019 Instrumental techniques in Drug Discovery
55/110
Nssamjn|miez ig MV
Gitvmdv \vnezgivkdl Megvnvdl MV- nel Vnkne Zsdj|vizjis}
nvd mksiv|ne| |iiaz giv |`d ziaml z|n|d j`nvnj|dvmn|mie ig
s`nvknjdt|mjna ziamlz nel giv |`d mlde|mgmjn|mie ig |`dmv
j`dkmjna z|vtj|tvdz%
i|`dv kd|`ilz giv ziaml z|n|d j`nvnj|dvmn|mie ig
s`nvknjdt|mjna ziamlz d%h% P+ vn} sixldv lmggvnj|mie! LZJ!
\H-%
j`nvnj|dvmn|mie ig sia}kivs`mzk nel ld|dj|mie me lvthsviltj|%
Fi|` kd|`ilz nvd nazi ztm|nfad giv |`d mlde|mgmjn|mie)
ld|dj|mie ig |`d sia}kivs`mj givk me |`d |nfad|%
44Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
56/110
Nssamjn|miez ig G\MV
Wdv} `mh` vdziat|mie vd~tmvdl+ Hnzditz
Kmp|tvdz
Z|tl} ig znksadz `nwmeh wdv} `mh` nfzivs|mie
|t } i znks dz x | xdn n zivs| ie ne z
Tzdl me svi|dme z|vtj|tvd ld|dvkmen|mie
Tzdl me j`nvnj|dvmmeh Nlvdeijnvjmeikn Wdv} zknaa znksad zmd?
If|nmemeh Vdgadj|mie zsdj|vn
MV dkmzzmie z|tl} 47Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
57/110
Nssamjn|miez ig Ednv MV
EMV? hiil sded|vn|mie svisdv|mdz Kmemkna znksad sded|vn|mie vd~tmvdl
\`mjb an}dvz jne fd nena}dl
^tne|m|n|mwd nena}zmz ig jiksitelz
jie|nmemeh gtej|miena hvitsz knld ig @
fieldl |i I! J! E
Ld|dvkmen|mie ig >3! 63! :3 nkmedz
48Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
58/110
Nssamjn|miez ig N\V+G\MV
Ztvgnjd nena}zmz ig fmiaihmjna z|vtj|tvdz
Kiem|ivmeh vdnj|mie svijdzzdz
Dwnatn|mie ig gdvkde|dl giilz
40Naamnejd
S` |m a am |m g
-
8/9/2019 Instrumental techniques in Drug Discovery
59/110
S`nvknjdt|mjna nssamjn|miez ig
Kml+MV nel Vnkne zsdj|vizjis} Kml+MV nel Vnkne zsdj|vizjis} nvd wdvzn|mad |iiaz me
s`nvknjdt|mjz nel fmis`nvknjdt|mjz! xm|` n xmld
gmdal ig nssamjn|miez vnehmeh gvik j`nvnj|dvmn|mie ig
lvth givktan|miez |i datjmln|mie ig bmed|mjsvijdzzdz me lvth ldamwdv}%
Edx ldwdaiskde|z me nssamjn|miez ig |`dzd kd|`ilz
giv z|tl}meh lvth ldamwdv} z}z|dkz%
G\MV+N\V mz n xdaa+dz|nfamz`dl z|nelnvl kd|`il tzdl
|i z|tl} lvth vdadnzd me zdkmziaml givktan|miez! lvth
sded|vn|mie! nel megatdejd ig sded|vn|mie kilmgmdvz2
m| mz nazi jnsnfad igme wmwi z|tlmdz% 4=Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
60/110
G\MV+SNZ s`i|i njitz|mj zsdj|vizjis}- `nz fdde nssamdl |i?
Kdnztvd lvth jie|de| me zdkmziaml nel ziaml givktan|miez!
Ld|dvkmed lvth sded|vn|mie me|i nv|mgmjmna nel fmiaihmjna
kdkfvnedz%
Vnkne zsdj|vizjis} jne fd tzdl |i?
J`nvnj|dvmd |`d z|vtj|tvd ig jiaaimlna lvth jnvvmdv z}z|dkz%
Me wmwi z|tlmdz%
djde }! dvd nz dde vdkde itz dj e jn ksviwdkde e
wmfvn|miena kmjvizsdj|vizjis}?
G\MV mknhmeh z`ixz hvdn| svikmzd me m|z nfmam|} |i wmztnamd
|`d lvth nel dpjmsmde| lmz|vmft|mie me s`nvknjdt|mjna
givktan|miez ztj` nz |nfad|z nel |`dvnsdt|mj |vnezldvkna
z}z|dkz! nz xdaa nz |i vdwdna |`d kdj`nemzk ig lvth vdadnzd%
Gtv|`dvkivd! |`mz tem~td |dj`em~td iggdvz jiksad|da} edx
sizzmfmam|mdz |i z|tl} |`d an|dvna lmggtzmie ig lvthz%
73Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
61/110
ETJADNV KNHED\MJ VDZIENEJD
ZSDJ\VIZJIS]
+ne mldna |iia giv Lmnheizmz 'Lvth Ldzmhe
7>Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
62/110
ME\VILTJ\MIE
FNZMJ SVMEJMSAD ME EKV
N|ikmj Etjadm |me} knhed|z
Me dp|dvena Knhed|mj Gmdal + naamhe iv issizd
Mg mvvnlmn|dl xm|` DKV ig svisdv gvd~tdej} Vdzienejd i
SNVNKD\DVZ
J`dkmjna z`mg|z
Zsme an||mjd vdanpn|mie |mkd
76Naamnejd
ETJADNV ZSME Z\N\DZ @]LVIHDE ETJADTZ
-
8/9/2019 Instrumental techniques in Drug Discovery
63/110
ETJADNV ZSME Z\N\DZ + @]LVIHDE ETJADTZ
" "
\`d zsme ig |`d sizm|mwda}
j`nvhdl etjadtz hdedvn|dz
n knhed|mj kikde| wdj|iv! k%k
" >)6 + >)6
\`d |xi z|n|dznvd d~tmwnade|
me dedvh} me |`d
nfzdejd ig n
knhed|mj iv ne
dadj|vmj gmdal%
k
\XI ZSME Z\N\DZ
7:Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
64/110
Z
N zsmeemeh etjadtz xm| m|(z knhed|mj gmdalnamhedl xm|` |`d knhed|mj gmdal ig n knhed|
+ zsme z|n|d!gnwivnfad!aixdv dedvh}
E
Z
E
E
Z + zsmez|n|d!tegnwivnfad!
`mh dv dedvh}
Nzsmeemeh etjadtz xm|`m|(zknhed|mj gmdalnamhedlnhnmez| | d knhed|mj gmdalig n knhed|
Z
E
D
Fi
D ; ` p :33 K@ D ; ` p 433 K@
8%34 \ >>%84 \
svi|ie zsme z|n|d(aixdv dedvh}-
svi|ie zsme z|n|d(`mh`dv dedvh}-
Hvns`mjna vdan|miez`ms fd|xdde
knhed|mj gmdal (Fi- nel gvd~tdej} (giv >@ EKV nfzivs|miez
n| ei knhed|mj gmdal!|`dvd mz ei lmggdvdejd fd|dde+ nel + z|n|dz%
3 \
7
-
8/9/2019 Instrumental techniques in Drug Discovery
65/110
VDZIENEJDVDZIENEJD
Nfzivs|mie ig dedvh} f} |`d zsmeemeh etjadtz
74Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
66/110
Vdzienejd
Vdzienejd? Kn|j`meh ig en|tvna gvd~tdej} xm|`
|`d nssamdl gvd~tdej}%
Me EKV |`d nssamdl vnlmi gvd~tdej} `nz |i fd
etjadm x`mj` mz |`d jiezd~tdejdz ig nssamdl
dp|dvena knhed|mj gmdal-
Nfzivs|mie ig vnlmi gvd~tdej} ijjtv f} etjadm
ng|dv vdzienejd mz nj`mdwdl%
77Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
67/110
Svdjdzzmiena gvd~tdej} (e-\`d etkfdv ig vdwiat|mie sdv zdjiel knld f}knhed|mj kikde| wdj|iv ig |`d etjadtz nvitel |`d dp|dvena
knhed|mj gmdal F3IV
Svdjdzzmiena gvd~tdej} mz d~tna |i |`d gvd~tdej} ig
edjdzznv} |i meltjd n |vnezm|mie gvik ied zsme z|n|d |i i|`dv%
78Naamnejd
E a Z m D A aE a Z m D A a
-
8/9/2019 Instrumental techniques in Drug Discovery
68/110
Etjadnv Zsme Dedvh} AdwdazEtjadnv Zsme Dedvh} Adwdaz
+>)6
Me n z|vieh knhed|mj
tenamhedl
E
Fi
">)6
i
zsme z|n|dz lmggdv me
dedvh}%
namhedl
Z 70Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
69/110
Nfzivs|mie ig Dedvh}Nfzivs|mie ig Dedvh}
+>)6 +>)6
~tne|mdl
Issizdl
Fi
">)6 ">)6
LD ; `e
LD
Vnlmigvd~tdej}
Nssamdl
Gmdal
Namhedl7=Naamnejd
\@D DEDVH] ZDSNVN\MIE LDSDELZ IE F\@D DEDVH] ZDSNVN\MIE LDSDELZ IE F
-
8/9/2019 Instrumental techniques in Drug Discovery
70/110
LD
+ >)6
; bF ; e
\@D DEDVH] ZDSNVN\MIE LDSDELZ IE F\@D DEDVH] ZDSNVN\MIE LDSDELZ IE Fii
Fi
" >)6
ldhdedvn|d
n| Fi ; 3
mejvdnzmeh knhed|mj gmdal z|vdeh|`
83Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
71/110
\`d\`d AnvkivAnvkiv D~tn|mieD~tn|mie
he ; 6s Fi
LD ; bFi ; `e jne fd |vnezgivkdl me|ih}viknhed|mj
vn|mi hgvd~tdej} ig
|`d mejikmeh
vnlmn|mie |`n| 6sh mz n jiez|ne| x`mj` mz lmggdvde| givdnj` n|ikmj etjadtz (@! J! E! d|j-
z|vdeh|` ig |`d
knhed|mj gmdal
xmaa jntzd n
|vnezm|mie
e Fi Z|viehdv knhed|mj gmdalz (Fi- jntzd|`d mez|vtkde| |i isdvn|d n| `mh`dvgvd~tdejmdz (e-%
8>Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
72/110
EKV Zmhenaz
\`d etkfdvig zmhenaz z`ixz `ix kne} lmggdvde|
bmelz ig svi|iez nvd svdzde|%
\`d aijn|mie ig |`d zmhenaz z`ixz `ix z`mdaldl iv
%
\`d me|dezm|} ig |`d zmhena z`ixz |`d etkfdv ig
svi|iez ig |`n| |}sd%
Zmhenazsam||mehz`ixz |`d etkfdv ig svi|iez ienlonjde| n|ikz%
86Naamnejd
LMGGDVDE\ \DJ@EM^TDZ
-
8/9/2019 Instrumental techniques in Drug Discovery
73/110
LMGGDVDE\ \DJ@EM^TDZ
Fnzdl ie etjadm
@> EKV
J>: EKV
G>: EKV ' S:> EKV
E>4 EKV ' I>8 EKV
JXEKV jie|metitz xnwd EKV-
G\EKV
6LYEKV ':LYEKV
JIZ] YJIVVDAN\MIE ZSDJ\VIZJIS]
KVMYKNHED\MJ VDZIENEJD MKNHMEH
DZVYDADJ\VIE ZSME VDZIENEJD ZSDJ\VIZJIS]
8:Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
74/110
NSSAMJN\MIEZ IG EKV ME KDLMJMED
JAMEMJNA NSSAMJN\MIE IG SVI\IE MKNHMEH MELMNHEIZMZ
FVNME Lmz|mehtmz`meh hvn} kn||dv ' x`m|d kn||dv
Mknhmeh siz|dvmiv gizznd! fvnme z|dk! zsmena jivl
Ld|dj| ldk}damen|meh adzmiez! |tkivz! `dkivv`nhdz!
megnvj|miez
NFLIKDE
-
8/9/2019 Instrumental techniques in Drug Discovery
75/110
NFLIKDE
i Kd|nfiamj amwdv lmzdnzd
i Kdnztvdz amwdv mvie iwdv ainl me `dkij`vikn|izmzi Gijna nvdnz ig megankkn|mie me j`viemj nj|mwd `dsn|mzmz
BMLED]Z
i Lmz|mehtmz`meh vdena jiv|dp ' kdltaan
SDAWMZ
i Lmggdvde|mn|dz fd|xdde Fdemhe sviz|n|mj `}sdvsanzmn
' sviz|n|mj jnvjmeikni Ld|dj|z fanlldv |tkitvz
84Naamnejd
ATEH
-
8/9/2019 Instrumental techniques in Drug Discovery
76/110
ATEHi Nzzdzzmeh nfeivknam|mdz
i Vdzsmvn|iv} hn|meh
@DNV\i \ikihvns`mj mknhdz ig `dnv| ktzjad! j`nkfdvz!
wnawtanv z|vtj|tvdz
i DJ@I+SANENV \DJ@EM^TDi Lmzjvmkmen|mie fd|xdde megnvj|dl! mzj`dkmj ' eivkna
k}ijnvlmtk
FVDNZ\i :L+EKV ' zmehad+zamjd sanenv mknhmeh me ld|dj|mehfvdnz| nfeivknam|mdz
87Naamnejd
KTZJTAI ZBDAD\NA Z]Z\DK
-
8/9/2019 Instrumental techniques in Drug Discovery
77/110
KTZJTAI ZBDAD\NA Z]Z\DK
Ldkiez|vn|dz Iz|di k}dam|mz! |tkiv kd|nz|nzmz me
wdv|dfvna filmdz ' sdawmj fiedz Mknhdz ig ktzjadz! |deliez! amhnkde|z
FAIIL WDZZDAZ ' GAIX
N|`dvizjadvi|mj wnzjtanv lmzdnzd Nzzdzz faiil gaix me knoiv wdzzdaz%
MEWMWI ZSDJ\VIZJIS]
J`dkmjna z`mg| s`deikdeie Lmnheizmz ig vnvd lmzdnzd |i mefive dvvivz+
Kj Nvladz z}elvikd
MEWMWI Nena}zmz ig Fied gaitvmld jie|de|%
-
8/9/2019 Instrumental techniques in Drug Discovery
78/110
EKV MKNHMEH Z\TLMDZ
Damkmen|dz vmzb ig p+vnlmn|mie
Dpjdaade| zsn|mna ' jie|vnz| vdziat|mie
Ld|dj|meh lmzdnzdz n| dnvamdv z|nhdz
80Naamnejd
EKV ME S@NVKNJDT\MJNA VDZDNVJ@
-
8/9/2019 Instrumental techniques in Drug Discovery
79/110
EKV ME S@NVKNJDT\MJNA VDZDNVJ@
Adnlmeh |dj`eiaih} giv :+L z|vtj|tvd ld|dvkmen|mieig fmi+knjvikiadjtadz
Z|tl}meh svi|dme z|vtj|tvd
ZNV f} EKV Eiwda adnl jiksitelz
|`d fmelmeh kildz nel zm|d sizm|miez
Kiadjtanv l}enkmjz! jiegivkn|miena nena}zmz
Z@NSDZ Adnl hdedvn|mie
EKV ZIAWD
8=Naamnejd
Z| | a m
-
8/9/2019 Instrumental techniques in Drug Discovery
80/110
Z|vtj|tvna hdeikmjz
Mlde|mg}meh hded sviltj|z me lmzdnzd
\nvhd|z ig lvth ldzmhe%
Ldwdaiskde| ig Eiwda lvth ldamwdv} z}z|dkz
De`nejmeh @\Z nzzn}z
\`itznelz ig jiksitelz
Jv}ihdemj EKV |dj`eiaih} ) jv}isvifdz
03Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
81/110
>%Mlde|mgmjn|mie ig z|vtj|tvna mzikdvz
6%Ld|dj|mie ig `}lvihde fielmeh
:%Ld|dj|mie ig nvikn|mjm|}
Naamnejd
EKV Eifda Svmd Antvdn|dz
-
8/9/2019 Instrumental techniques in Drug Discovery
82/110
EKV Eifda Svmd Antvdn|dz \`d Eifda Svmd me S`}zmjz >==46+ MzmlivO% Vngm!TZN
Lmzjiwdv} ig edx kd|`ilz giv etjadnv knhed|mjsvdjmzmie
\`d Eifda Svmd me J`dkmz|v >==> Gdamp Faij` TZNnel Dlxnvl K% Stvjdaa! TZN Kd|`iliaih} ig `mh`vdziat|mie EKV%
\`d Eifda Svmd me J`dkmz|v} 6336 Btv| Xt|`vmj`!
Zxm|dvanel Ld|dvkmemeh :+L Z|vtj|tvd f} EKV% \`d Eifda Svmd me Kdlmjmed 633: Snta J% Ant|dvftv!
TZN nel Sd|dv Knez gmdal! T%B% Lmzjiwdvmdzjiejdvemeh KVM%
06Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
83/110
0:Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
84/110
Me|viltj|mie
Knzz zsdj|vikd|v} mz dksai}dl |i nena}d
jikfmen|ivmna amfvnvmdz! zd~tdejd fmikiadjtadz!
Z|vtj|tvd datjmln|mie ig tebeixez!
Dew viekde|n ne ivdez j nen }| jz!
^tnam|} jie|via ig lvthz! ganwivz nel sia}kdvz
0
-
8/9/2019 Instrumental techniques in Drug Discovery
85/110
\`d fnzmj svmejmsad ig knzz zsdj|vikd|v} (KZ-?
\i hdedvn|d miez gvik dm|`dv meivhnemj iv ivhnemj
jiksitelz f} ne} ztm|nfad kd|`il!
\i zdsnvn|d |`dzd miez f} |`dmv knzz+|i+j`nvhd vn|mi k)-
Nel |i ld|dj| |`dk ~tnam|n|mwda} nel ~tne|m|n|mwda} f}
|`dmv vdzsdj|mwd k) nel nftelnejd%
Fdzmldz dadj|viez! n|ikmj- miez iv s`i|iez! dedvhd|mj
dggdj| miemn|mie ig |`d nena}|d%
\`d |mkd+ig+gamh`| \IG- nena}dv! mie zdsnvn|mie f} k)
jne fd dggdj|dl me gmdal gvdd vdhmiez! |ii! sviwmldl |`d miez
sizzdzz n xdaa ldgmedl bmed|mj dedvh} n| |`d de|vnejd ig
|`d gamh`| sn|`%
\`d nena}|d kn} fd miemdl |`dvknaa}! f} dadj|vmj gmdalz iv
f} mksnj|meh dedvhd|mj dadj|viez! miez iv s`i|iez%04Naamnejd
Nssamjn|mie ig ALM (Anzdv Ldzivs|mie)Miemn|mie-
-
8/9/2019 Instrumental techniques in Drug Discovery
86/110
Nssamjn|mie ig ALM (Anzdv Ldzivs|mie)Miemn|mie-
ALM ig sds|mldz nel iamhiznjj`nvmldz
ALM mz ktj` fd||dv ztm|dl giv |`d nena}zmz ig ivhnemj nel meivhnemjzna|z
Kiadjtadz xm|` anvhd jieothn|dl +dadj|vie z}z|dkz
Ivhnemj l}dz nz jie|nmedl me fnaa sime| mebz
Siv ` vmez
TW amh`|+nfzivfmeh z}e|`d|mj sia}kdvz
ALM svdzde|z n tzdgta na|dven|mwd |i KNALM me |`d aix+knzz vnehd%
Me nllm|mie! ziawde| gvdd znksad svdsnvn|mie jne fd dksai}dl
xm|` meziatfad nena}|dz%
@ixdwdv! ALM mz n `nvldv kd|`il |`ne KNALM nel
gvnhkde|n|mie
07Naamnejd
N am |m g KNALM
-
8/9/2019 Instrumental techniques in Drug Discovery
87/110
Nssamjn|miez ig KNALM
>% KNALM+KZ ig Z}e|`d|mj Sia}kdvz?6% Gmehdvsvme|z f} KNALM+KZ
:% Jnvfi`}lvn|dz f} KNALM+KZ
-
8/9/2019 Instrumental techniques in Drug Discovery
88/110
} } s }
fdjntzd m| tztnaa} sviwmldz ziada} me|nj| nel zmeha} j`nvhdl
~tnzmkiadjtanv miez iwdv ne dzzde|mnaa} teamkm|dl knzz vnehd%
X`mad sianv sia}kdvz ztj` nz sia} (kd|`}akd|`njv}an|d- (SKKN-!sia}d|`}aded ha}jia (SDH-! nel i|`dvz vdnlma} givk RK"@[" iv
RK"nabnam[" miez!
Eiesianv sia}kdvz ambd sia}z|}vded (SZ- eie+gtej|mienamdl
sia}kdvz ambd sia}d|`}aded (SD- jne iea} fd jn|miemdl f} |vnezm|mie
kd|na miez me |`dmv >" ipmln|mie z|n|d%
\`d givkn|mie ig dwdea} zsnjdl iamhikdv mie zdvmdz jne nazi fd
dksai}dl |i dz|nfamz` ne me|dvena knzz jnamfvn|mie ig n zsdj|vtk%
\`d kiz| mksiv|ne| snvnkd|dvz |`n| jne fd ld|dvkmedl f} KNALM
nvd etkfdv+nwdvnhd kiadjtanv xdmh`| (Ke-
xdmh`|+nwdvnhd kiadjtanv xdmh`| (Kx-
kiadjtanv xdmh`| lmz|vmft|mie dpsvdzzdl nz sia}lmzsdvzm|} (SL-
00Naamnejd
Nssamjn|mie ig Dadj|vizsvn} Miemn|mie
-
8/9/2019 Instrumental techniques in Drug Discovery
89/110
Nssamjn|mie ig Dadj|vizsvn} Miemn|mie
DZM ig Zknaa Kiadjtadz (sianv nena}|dz-
Sds|mld nel svi|dme j`nvnj|dvmn|mie mejatlmeh |`dmv jiksad|d
zd~tdejmeh
DZM mz nssamdl |i Kd|na Jiksadpdz (miemj- nel vdan|dl
jiksitelz
i tv nj ne z? n ie j! ne ie j ne eie+ ie j ztv nj ne z
nvd vdnlma} ld|dj|dl f} DZM
Iamhietjadi|mldz! LEN! nel VEN nvd fdz| nena}dl f}
edhn|mwd+mie DZM
DZM ig Iamhiznjj`nvmldz nel jaizda} vdan|dl jiksitelz ztj`
nz ha}jisvi|dmez! hnehamizmldz! amsiznjj`nvmldz d|j% sdvkm|z
kiadjtanv xdmh`| ld|dvkmen|mie nel z|vtj|tvd datjmln|mie
0=Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
90/110
AJ+KZ Nssamjn|miez me
lvth ldwdaiskde|
=3Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
91/110
AJ+KZ Nssamjn|miez me lvth ldwdaiskde|
Ldwdaiskde| Z|nhd AJ)KZ nena}zmz nj|mwm|mdz
Lvth lmzjiwdv} Svi|dme mlde|mgmjn|mie2 en|tvna sviltj|z
mlde|mgmjn|mie2 kd|nfiamj z|nfmam|} svigmadz2
kiadjtanv xdmh`| ld|dvkmen|mie giv
jikfmen|ivmna)kdlmjmena j`dkmz|v} ztssiv|
=>
Svdjamemjna
ldwdaiskde|
Mkstvm|}! ldhvnlne|! nel kd|nfiam|d
mlde|mgmjn|mie
Jamemjna
ldwdaiskde|
^tne|m|n|mwd fminena}zmz2 z|vtj|tvd mlde|mgmjn|mie
Knetgnj|tvmeh Mkstvm|} nel ldhvnlne| mlde|mgmjn|mie
Naamnejd
AJ+KZ Nssamjn|miez me
-
8/9/2019 Instrumental techniques in Drug Discovery
92/110
ss
Lvth Lmzjiwdv}
=6Naamnejd
Sds|mld Knssmeh
-
8/9/2019 Instrumental techniques in Drug Discovery
93/110
s ss h>% Sds|mld Knssmeh?
\`d mlde|mgmjn|mie ig svi|dmez mz dzzde|mna giv teldvz|nelmehfmiaihmjna svijdzz nel |`d gtej|mie ig |`d svi|dme ltvmeh
eivkna nel lmzdnzd z|n|dz%
\`d vdzta|meh mezmh`|z adnl |i |`d ldwdaiskde| ig |`dvnsmdz
giv me|dvwde|mie! nel ta|mkn|da}! |`d jtvd ig lmzdnzd% \`d
e ivkn ie ne eix d hd dv wd vik z }sd i z t }
nvd dp|vdkda} wnatnfad giv nj|mwm|mdz mewiawdl xm|` |nvhd|
mlde|mgmjn|mie nj|mwm|mdz ltvmeh lvth lmzjiwdv}%
\xi+lmkdezmiena hda dadj|vis`ivdzmz 6+LHD- mz |`d svmknv}
nena}zmz |iia tzdl me |`d s`nvknjdt|mjna meltz|v} |i
j`nvnj|dvmd |`d dpsvdzzmie ig svi|dmez% Knzz zsdj|vikd|v}+
fnzdl kd|`ilz nvd dkdvhmeh nz ne mksiv|ne| snv|edv xm|` 6+
LHD giv jivvdan|meh svi|dmez |i |`dmv gtej|mie%
=:Naamnejd
Sds|mld Knssmeh
-
8/9/2019 Instrumental techniques in Drug Discovery
94/110
Mlde|mgmjn|mie zj`dkdz |`n| mewiawd AJ)KZ nel
KNALM+\IG |dj`em~tdz `nwd fdde nssamdl |i n fvinlvnehd ig dwde|z |`n| mewiawd svi|dmez ztj` nz
jiwnade| kilmgmjn|mie! svi|dia}|mj jadnwnhd! nel
fmelmeh%
s ss h
t }! t
j`nvnj|dvmn|mie mz ie gitv lmz|mej| hinaz?
>- jiegmvkn|mie ig st|n|mwd zd~tdejd2
6- mlde|mgmjn|mie ig nkmei njml kilmgmjn|miez2 :- mlde|mgmjn|mie ig beixe svi|dmez2
-
8/9/2019 Instrumental techniques in Drug Discovery
95/110
} s ss h
Zmkmanv nena}zmz z|vn|dhmdz jne fd nssamdl giv |`d
sds|mld knssmeh ig ha}jisvi|dmez jikfmedl me+zitvjd jiaamzmienaa} meltjdl lmzzijmn|mie JML- xm|`
AJ)KZ)KZ |i mlde|mg} zm|dz ig E+ nel I+amebdl
ha}jiz}an|mie% \`mz eiwda nssvinj` tzdz n zdvmdz ig
sds|mld knsz nel |i zdadj|mwda} zjvdde giv
ha}jisvi|dmez%
\`d kd|`il mz fnzdl ie |`d j`nvnj|dvmz|mjgvnhkde|n|mie ig ha}jisvi|dmez |i givk n E+
njd|}a`dpiznkmed @dpENj"- gvnhkde| mie n| k)
63
-
8/9/2019 Instrumental techniques in Drug Discovery
96/110
N kmp|tvd ig sds|mldz nel ha}jisds|mldz mz hdedvn|dl x`de
|`d ha}jisvi|dme mz vdltjdl! nab}an|dl! nel de}kn|mjnaa}
lmhdz|dl%
N zdvmdz ig |`vdd zdsnvn|d dpsdvmkde|z! mz tzdl |i mlde|mg} |`d
E+ nel I+amebdl ha}jisds|mldz%
>% \`d gmvz| dpsdvmkde| tzdz AJ)KZ |i sviwmld n kns ig |`d
sds|mld siv|mie ig |`d svi|dme nel |i melmjn|d |`d svdzdejd
%
6% \`d zdjiel dpsdvmkde| mewiawdz |`d tzd ig AJ)KZ)KZ |i
zjvdde |`d kmp|tvd giv jiksitelz |`n| gvnhkde| |i }mdal |`d
lmnheiz|mj k) 63< @dpENj"-% E+ nel I+amebdl ha}jisds|mldz
nvd fi|` mlde|mgmdl%
:% N gmena dpsdvmkde| mz sdvgivkdl ie n znksad |vdn|dl xm|`
sds|mld E?ha}jizmlnzd G SEHnzd G- |i vdadnzd |`d E+amebdl
iamhiznjj`nvmldz nel |i mlde|mg} |`d I+amebdl ha}jisds|mldz
dpjatzmwda}% =7Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
97/110
=8Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
98/110
Nllm|miena z|vtj|tvna nena}zmz ig ha}jisvi|dmez
hdedvnaa} vd~tmvdz gvnhkde|n|mie f} j`dkmjna
iv de}kn|mj jadnwnhd nel f} zdsnvn|mie iv
mzian|mie% Ie+amed AJ)KZ kd|`ilz sviwmld ne
=0Naamnejd
En|tvna Sviltj|z Ldvdsamjn|mie
-
8/9/2019 Instrumental techniques in Drug Discovery
99/110
En|tvna Sviltj|z Ldvdsamjn|mie En|tvna sviltj|z iggdv n zitvjd ig tem~td j`dkmjna lmwdvzm|}
giv |`d s`nvknjdt|mjna meltz|v}% Lvthz ldvmwdl gvik en|tvna sviltj|z `nwd fdde me|viltjdl giv
|`d |vdn|kde| ig jnejdv! mkkteiztssvdzzmie! jnvlmiwnzjtanv
|`dvns}! nel ne|m+megdj|mwd |`dvns}%
Kiz| ne|mfmi|mjz jikd gvik zdjielnv} kd|nfiam|dz ig zimakmjviivhnemzkz |`n| me`mfm| fnj|dvmn iv gtehm% Anvhd zjnad
zjvddemeh ig kmjviivhnemzk gdvkde|n|miez giaaixdl f}
mzian|mie nel z|vtj|tvd datjmln|mie mz vd~tmvdl%
Fdjntzd kne} en|tvna sviltj|z `nwd fdde svdwmitza}mlde|mgmdl! nssvinj`dz |`n| nwiml |mkd+jieztkmeh mzian|mie
nel sviwmld ~tmjb datjmln|mie nvd dzzde|mna%
==Naamnejd
n edx z|vn|dh} xnz me|viltjdl f} Njbdvknee d| na% |`n| tzdz
-
8/9/2019 Instrumental techniques in Drug Discovery
100/110
n edx z|vn|dh} xnz me|viltjdl f} Njbdvknee d| na% |`n| tzdz
ne ie+amed DZMAJ)KZ nssvinj` |`n| me|dhvn|dz kta|m+
jiksiede| mlde|mgmjn|mie! gvnj|mie jiaadj|mie! nel znksad
svdsnvn|mie giv fminj|mwm|} zjvddemeh >==7-%
Tzmeh |`mz AJ)KZ fnzdl nssvinj`! jvtld dp|vnj|z nvd zjvddedl
xm|`it| dp|dezmwd stvmgmjn|mie nel j`dkmjna nena}zmz%
Adzz kn|dvmna mz vd~tmvdl ltd |i |`d zdezm|mwm|} ig |`d
%
\`mz vdziat|mie xital ivlmenvma} fd vdan|mwda} siiv xm|` n
gvnj|mie jiaadj|mie svijdzz% Gtv|`dvkivd! fdjntzd |`d DZM nj|z
nz n jiejde|vn|mie+ ldsdelde| ld|dj|iv! |`d @SAJ dggatde| jne
fd zsam| fd|xdde knzz zsdj|vikd|v} nena}zmz nel gvnj|miejiaadj|mie% \`tz! kiadjtanv xdmh`| megivkn|mie mz if|nmedl!
nel nssvipmkn|da} =3$ ig |`d gvnj|mien|dl kn|dvmna mz
vdjiwdvdl giv fmiaihmjna |dz|meh%
>33Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
101/110
>3>Naamnejd
Fminggmem|} Zjvddemeh
-
8/9/2019 Instrumental techniques in Drug Discovery
102/110
} h Jikfmen|ivmna j`dkmz|v} `nz j`nehdl |`d z|vn|dh} ig lvth
jnelmln|d z}e|`dzmz% Nz n vdzta|! `telvdlz ig |`itznelz ig
jiksitelz nvd eix zjvddedl nhnmez| n snv|mjtanv fmiaihmjna |nvhd|%
Iejd nj|mwm|} mz ld|dvkmedl giv n kmp|tvd! |`d mlde|mgmjn|mie ig |`d
nj|mwd jiksiede|z- mz edjdzznv}% @ixdwdv! |`mz nssvinj` vd~tmvdz
n jiezmldvnfad nkite| ig vdzitvjdz%
\i vdltjd |`d |mkd nel vdzitvjdz vd~tmvdl giv zjvddemeh |`d anvhdetkfdv ig jiksitelz sviltjdl f} jikfmen|ivmna j`dkmz|v}!
nssvinj`dz gdn|tvmeh |`d snvnaada zjvddemeh ig kmp|tvdz ig
jiksitelz 63:3- `nwd fdde mewdz|mhn|dl% \`d vdjde| z|tlmdz
sdvgivkdl f} Neldvdhh nel jixivbdvz ldzjvmfd |`d tzd ig
fminggmem|} zdadj|mie AJ)KZ kd|`ilz giv |`d mlde|mgmjn|mie ig nj|mwdkmp|tvd jiksiede|z- Lnwmz d| na%! me svdzz-% \`mz nssvinj` gdn|tvdz
ne me|dhvn|dl fminggmem|} fnzdl AJ)KZ zjvddemeh kd|`il |i
zdsnvn|d nel mlde|mg} Adnl jiksitelz gvik kmp|tvdz%
>36Naamnejd
-
8/9/2019 Instrumental techniques in Drug Discovery
103/110
>3:Naamnejd
Me Wmwi Lvth Zjvddemeh
-
8/9/2019 Instrumental techniques in Drug Discovery
104/110
\dj`eiaih} giv nt|ikn|dl `mh`|`vith`st| fminena}zmz%
gijtzdl ie kd|`ilz giv ld|dvkmemeh kta|mjiksiede|kmp|tvdz ig lvth jnelmln|dz |`n| mewiawd s`nvknjibmed|mjz
nel kd|nfiamj z|nfmam|}%
\`dzd nj|mwm|mdz xdvd sdvgivkdl ltvmeh |`d svdjamemjna nel
jamemjna z|nhdz ig lvth ldwdaiskde|%
\`d eddl |i sviwmld ne dnva} nzzdzzkde| ig |`dzd svisdv|mdz
vdzta|dl me edx z|vn|dhmdz giv me wmwi lvth zjvddemeh ltvmeh
|`d lvth lmzjiwdv} z|nhd%
AJ)KZ)KZ nssvinj`dz! tzmeh vdan|mwda} zmksad mzian|mie nel
j`vikn|ihvns`} jielm|miez! svdzde| ne dggdj|mwd nssvinj` |i
dwnatn|d edx adnl jiksitelz giv ztfzd~tde| ldwdaiskde|
iv zdadj|mie ig ne is|mkna lvth jnelmln|d xm|`me n zsdjmgmj
|`dvnsdt|mj nvdn iv n |nvhd|dl janzz ig jiksitelz%>3
-
8/9/2019 Instrumental techniques in Drug Discovery
105/110
} h Vdjde|a}! |`d tzd ig gnz| hvnlmde| dat|mie AJ)KZ |dj`em~tdz
xnz ldzjvmfdl giv `mh` |`vith`st| kd|nfiamj z|nfmam|}zjvddemeh Njbdvknee d| na%! >==0-% \`d kd|`il tzdz n @SAJ
jiatke+zxm|j`meh nssnvn|tz |i ldzna| nel nena}d adnl
jnelmln|dz mejtfn|dl xm|` `tkne amwdv kmjvizikdz%
\`d vnsml z|vtj|tvd mlde|mgmjn|mie ig kd|nfiam|dz tzmeh
x ne ie vns knzz zsdj vikd dv isd d n %!
>==0-%
Me |`mz z|tl}! kd|nfiamj z|nfmam|} nena}zmz mz nt|ikn|dl |i
sviwmld knpmktk z|vtj|tvna megivkn|mie me jikfmen|mie xm|`
svdlmj|mwd z|vn|dhmdz giv fmi|vnezgivkn|mie%
>34Naamnejd
\`mz gdn|tvd mz tem~td nel nwimlz |`d kta|msad (6
-
8/9/2019 Instrumental techniques in Drug Discovery
106/110
~ s ( -
meodj|miez |`n| nvd edjdzznv} xm|` i|`dv KZ)KZ
jiegmhtvn|miez d%h%! |neldk ~tnlvtsiad-%
Naieh xm|` |`d zmhemgmjne| znwmehz me |mkd! ld|nmadl z|vtj|tvd
megivkn|mie mz hdedvn|dl! x`mj` denfadz n jiksvd`dezmwd
nena}zmz ig ztfz|vtj|tvd vdan|miez`ms |i fd jiez|vtj|dl giv
dnj` kd|nfiam|d%
lvth lmzjiwdv}! nel sviwmld ne dnva} sdvzsdj|mwd ie |`d
kd|nfiamjnaa} anfmad zm|dz! iv cczig| zsi|z(( ig n lvth jnelmln|d%
\`mz beixadlhd mz tzdgta ltvmeh adnl is|mkmn|mie nj|mwm|mdz!
nel jne adnl |i |`d mem|mn|mie ig svinj|mwd vdzdnvj` dggiv|z |`n|ldna xm|` kd|nfiamzk+htmldl z|vtj|tvna kilmgmjn|mie nel
|ipmjm|}%
>37Naamnejd
Nssamjn|miez ig AJ)KZ
-
8/9/2019 Instrumental techniques in Drug Discovery
107/110
me Svdjamemjna Ldwdaiskde|%
>38Naamnejd
Nssamjn|mie ig AJ)KZ me
-
8/9/2019 Instrumental techniques in Drug Discovery
108/110
Jamemjna Ldwdaiskde|
>30Naamnejd
Nssamjn|miez ig AJ)KZ me
-
8/9/2019 Instrumental techniques in Drug Discovery
109/110
Knetgnj|tvmeh
>3=Naamnejd
Nssamjn|miez ig AJ KZ
-
8/9/2019 Instrumental techniques in Drug Discovery
110/110
Nssamjn|miez ig AJ+KZ
>% \ipmjiaihmjna z|tlmdz! gmelmeh lvthz nel |ipmez me
wnvmd|} ig kn|dvmnaz xm|` zknaadv znksad wiatkd
6% Tvmed nena}zmz giv |ipmjiaih}
:% Li d |dz|? li me n de|z nel lvt z ig nftzdz|dvimlz! lmtvd|mjz-
top related