Peptide Structure: The Building Blocks of Life

Peptides are short polymers of amino acids linked by peptide (amide) bonds.

What is an amino acid?

o An amino acid is a molecule containing… an amine group a carboxylic acid a side chain (R-varies)

• There are 20 standard amino acids (standard meaning that they are directly coded for by DNA)

All except Proline are primary amines.

All have a stereocenter with R-configuration at the alpha carbon Except Cysteine, which has an S- configuration. Except Glycine which is achiral (i.e. has no stereocenter).

α­carbon

• Amino acids have varying side chains (R), and thus are categorized by their side chains.

Hydrophilic vs. Hydrophobic

o This property is determined by the polarity of the side chain.

“Like dissolves Like” • Polar - Hydrophilic • Non-Polar – Hydrophobic

Acidic vs. Non-acidic vs. Basic o This property is determined by comparison to water

(pka=15.7)

• More acidic than water: Acidic • Lone pairs ready to accept a proton: Basic • Every thing else: Non-acidic

What is a Peptide bond?

o A Peptide bond links two amino acids together.

Formed when the carboxyl group of one amino acid reacts with the amine group of another amino acid.

One molecule of water is released per bond formed.

o Peptide bonds provide stability.

Torsional Strain: Cis vs. Trans

• Equilibrium favors Trans: The largest groups are furthest apart.

Conjugation: Peptide bond

• Creates a Barrier to Rotation • Every conjugated atom and those

directly bonded to them, stay Planar.

• This creates multiple flat areas (not all in the same plane) within the peptide molecule, stabilizing the Peptide structure.

Peptide Structure is classified into four levels:

Primary Structure Secondary Structure Tertiary Structure Quaternary Structure

Primary Structure:

o Refers to the sequence in which the amino acids are bonded from N-terminus to

C-terminus.

Gly Ser Val

Secondary Structure:

o Intramolecular Hydrogen bonds cause three different motifs: α-Helix β-Sheet Coil

• α-Helix

Clockwise spiral down

Hydrogen Bonds between the carboxyl oxygen and the amine hydrogen 4 residues away.

Side chains point away from the coil

• β-Sheet

C‐Terminus

N‐Terminus

Hydrogen Bonds not

always parallel to each other.

Side chains stick out above

and below the chain.

More rigid and less elastic than α-Helix.

• Coil

• Not Random, just complicated.

Tertiary Structure:

o 3D positions of atoms in space. • Determined by the side chain and how it interacts with the

environment. Hydrophilic side chain:

• Polar environment: points out • Non polar environment: points in

Hydrophobic side chain: • Polar environment: points in • Non polar environment: points out

C‐Terminus

N‐Terminus

N‐Terminus

N‐Terminus

o Disulfide Bonds impact the 3D structures of proteins.

Form a loop in one chain Bond two separate chains

• ONLY CYSTINE forms disulfide bonds because a sulfur-hydrogen bond is required.

Quaternary Structure:

o Association of subunits (i.e. proteins etc.) by Non covalent Molecular Bonds:

• Hydrogen Bonds • London Forces

References Chemistry 14C Lecture supplement Images: Google and ChemDoodle Wikipedia http://en.wikipedia.org/wiki/Amino_acid

http://en.wikipedia.org/wiki/Peptide