Structure and Properties of Peptides: Biochemistry Study Notes

Study Guide - Smart Notes

Tailored notes based on your materials, expanded with key definitions, examples, and context.

Structure and Properties of Peptides

Peptide Bond Formation

The peptide bond is a fundamental linkage in biochemistry, connecting amino acids to form peptides and proteins. It is formed through a condensation reaction, which results in the loss of a water molecule.

Condensation Reaction: The carboxyl group of one amino acid reacts with the amino group of another, releasing H2O and forming a peptide bond.
General Reaction:
N-terminus: The end of the peptide with a free amino group.
C-terminus: The end of the peptide with a free carboxyl group.
Amino Acid Residues: Once incorporated into a peptide, amino acids are referred to as residues.
Example: Formation of a dipeptide from two amino acids.

Chemical Features and Structure of the Peptide Bond

The peptide bond exhibits unique chemical properties due to its partial double-bond character, which influences protein structure and function.

Planarity: Six atoms involved in the peptide bond (C, O, N, H, and two α-carbons) lie in the same plane due to resonance.
Partial Double-Bond Character: Resonance between the carbonyl oxygen and the amide nitrogen restricts rotation around the C-N bond.
Bond Angles: Typical bond angles are approximately 120°, consistent with sp2 hybridization.
Resonance Structures: The peptide bond can be represented by two resonance forms, contributing to its stability.
Equation:

Cis and Trans Conformations of the Peptide Bond

The peptide bond can exist in either cis or trans conformations, defined by the relative positions of the α-carbons adjacent to the bond.

Trans Conformation: Favored in most peptide bonds; α-carbons are on opposite sides of the C-N bond.
Cis Conformation: Less common; α-carbons are on the same side of the C-N bond.
Proline Exception: The amino acid proline is more likely to form cis peptide bonds, with a trans:cis ratio of about 4:1 in proteins.
Example: Structural diagrams showing trans and cis conformations.

Peptide and Protein Nomenclature

Peptides and proteins are named according to the sequence of amino acid residues from the N-terminus to the C-terminus.

Reading Sequence: Always read from N-terminal (left) to C-terminal (right).
Naming Convention: For short peptides, the suffix "-ine" or "-ate" is replaced with "-yl" (e.g., serine → seryl, alanine → alanyl).
Exceptions: For glutamine (Gln) and asparagine (Asn), the final "e" is dropped and replaced with "yl".
Example: A tripeptide sequence Ser-Ala-Val is named seryl-alanyl-valine.

Drawing Peptides in Two Dimensions

Peptides can be represented in two dimensions by illustrating the backbone and side chains.

Backbone: Draw the N–Cα–C=O sequence for each residue.
Hydrogen Atoms: Add H atoms to the N and Cα atoms.
Side Chains: Attach the appropriate R groups to each Cα.
Charge Representation: Indicate formal charges at the N- and C-termini and on ionizable side chains.
Example: Diagrams of the tripeptide ASV (Ala-Ser-Val) in both full atom and "chicken wire" formats.

Classification of Peptides and Proteins

Peptides and proteins are classified based on the number of amino acid residues.

Oligopeptide: Short chains of amino acids (typically < 15 residues).
Polypeptide: Chains with more than 15 amino acids.
Protein: Long polypeptide chains that fold into specific three-dimensional structures.

Ionizable Groups and pKa Values in Proteins

Proteins contain several ionizable groups, each with characteristic pKa values that influence the molecule's charge at different pH levels.

Group	Typical pKa Range
Terminal carboxyl	3.5–4.0
Side chain carboxyl (Asp, Glu)	4.0–4.8
Imidazole (His)	6.5–7.4
Thiol (Cys)	8.5–9.0
Phenolic (Tyr)	9.5–10.5
Terminal amino	8.0–9.0
Side chain amino (Lys)	9.8–10.4
Guanidino (Arg)	~12

Calculating the Isoelectric Point (pI) of Peptides

The isoelectric point (pI) is the pH at which a peptide or protein has a net zero charge. It is determined by the pKa values of the ionizable groups.

Step 1: List all pKa values for ionizable groups in the molecule, ranked from lowest to highest.
Step 2: Draw the molecule at pH = 0 (all possible protons present) and determine the net charge (n).
Step 3: Find the nth and (n+1)th pKa values in the ranked list.
Step 4: Average these two pKa values to determine the pI.
Equation:
Example: For EGAK tetrapeptide, pKa values are 1.8, 4.2, 7.8, 10. Net charge at pH 0 is +2, so pI = (4.2 + 7.8)/2 = 6.0.

Titration Curves of Peptides and Proteins

Titration curves illustrate how the net charge of a peptide or protein changes with pH, reflecting the ionization of various groups.

Isoelectric Point (pI): The pH at which the net charge is zero.
Net Positive Charge: At pH below pI, the molecule is positively charged.
Net Negative Charge: At pH above pI, the molecule is negatively charged.
Zwitterion: A molecule with both positive and negative charges but a net charge of zero.
Application: pI is important for techniques such as ion exchange chromatography.

Summary Table: Peptide Bond Properties

Property	Description
Formation	Condensation reaction between amino acids
Planarity	6 atoms in the same plane due to resonance
Conformation	Trans favored; cis more common in proline
Nomenclature	Named from N- to C-terminus; "-yl" suffix
pI Calculation	Average of relevant pKa values
Titration Curve	Shows net charge vs. pH

Additional info: Stereochemistry is important in peptide structure but is not always shown in simplified diagrams. The ability to draw and interpret peptide structures is essential for understanding protein function and biochemical techniques.