amino acids and peptides the “lego” of proteins. amino acids same general structure called alpha...
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Amino acids and peptides
The “Lego” of proteins
Amino Acids
• Same general structure
• Called alpha amino acids
• L- isomer is physiologically active
• Side chain or R group determines other properties
• Acid-base properties
H3N+
R
O
O
Amino Acids, General
• pK of carboxyl group around 2.3– Deprotonated at physiological pH
• R – COO-
• pK of amino group around 9.5 – Protonated at physiological pH
• H3N+-R
• Some R-groups are acidic or basic
Nonpolar amino acids
NH3+CH
O
CH3
O
NH3+CH2
O
O
NH3+
CH2
CH
O
CH3 CH3
ONH3+
CH CH2
O
CH3
CH3
O
N+
O
O
HH
glycine(G) Alanine (A)
NH3+
CH3
O
O
CH3
Valine (V)
Leucine (L)
Isoleucine (I)
Proline (P)
Aromatic Amino Acids
H3N+O
O
H3N+
O
N
O
H3N+
O
OH
O
phenylalanine (F) tyrosine (Y)
pKr = 10.07
tryptophan (W)
Polar Amino Acids, alcohols
H3N+
OH
O
O H3N+
CH3 OH
O
O
Serine (S) Threonine (T)
Polar Amino Acids(sulfur containing)
H3N+O
SH
O
N3N+O
SCH3
O
Cysteine (C)
Methionine (M)
Polar amino acids (amides)
H3N+ O
O
NH2
O
H3N+O
ONH2
O
Asparagine (N)
Glutamine (Q)
Charged Amino Acids (Acidic)
H3N+ O
O
O
O
H3N+O
OO
O
Aspartate (D)
Glutamate (E)pKr = 3.86
pKr = 4.25
Charged Amino Acids (Basic)
H3N+O
NH
NH2+NH2
O
H3N+O
N
NH
OH3N+
O
NH3+
O
Arginie (R)
pKr = 12.48
Histidine (H)
pKr = 6.0
Lysine (K)
pKr = 10.53
Titration of Amino acids
• Titration of glycine
Titration of Glutamate
H3N+O
OO
O
Glutamate (E)
pKr = 4.25
pK = 2.19
pK = 9.67
Purification of amino acids
• Chromatography– Various types– Ion exchange
• Uses net charge or can change with pH– Separate K, D and A
– HPLC
Electrophoresis
• Using electricity to move particles through a gelatinous matrix
• Isoelectric point
• IEF
Peptides
• Peptide bond is amide linkage between amino acids• No free rotation about C-N bond due to partial double
bond character of bond– resonance
NH
O
R2
H3N+
O
R1
O
N
O
R2
H3N+
O
R1
O
-
peptide bond
+
Peptides
• Peptides are vectorial– Have N and C termini
• Sequences read H3N+---COO-
P-I-G
NH
OH2N+
O
NH
O
O
Draw a tetrapeptide of L-A-R-D at physiological pH
• Answer
Biologically Interesting Peptides
• Aspartame– L-aspartyl-Lphenylalanine methyl ester
NH
OH3N+
O
OO
OCH3
Other small interesting peptides
• Enkephalins Y-G-G-F-LY-G-G-F-M
• OxytocinC-Y-I-Q-N-C-P-L-G-NH2
• Has C—C disulfide
• VasopressinC-Y-F-Q-N-C-P-R-G-NH2
• Also disulfide
Chemical Synthesis of Peptides
• Why?
• Done solid phase– Problem with in solution
• Hard to make pure desired sequence
– Purify by filtration
• Side chains blocked
• Made backwards ( C---N)
Scheme for peptide synthesis
Tetrapeptide answer
NH
OH3N+
O
NH N
H
O
O
O
O
O
NH
NH2H2N+
L A R D
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