Amino Acids and Peptides: Structure, Properties, and Classification

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5.1 Amino Acids

Structure of an α-Amino Acid

Amino acids are the building blocks of proteins, each containing a central α-carbon atom bonded to an amino group, a carboxylic acid group, a hydrogen atom, and a unique side chain (R group). The arrangement of these groups determines the chemical properties and reactivity of each amino acid.

α-Carbon: The central carbon atom to which all functional groups are attached.
Amino Group (-NH2): Acts as a base and can accept a proton.
Carboxylic Acid Group (-COOH): Acts as an acid and can donate a proton.
R Group (Side Chain): Unique to each amino acid and determines its identity and properties.
Zwitterion: At neutral pH, the amino group is protonated and the carboxylic acid group is deprotonated, resulting in a molecule with both positive and negative charges.

Example: Glycine is the simplest amino acid, with its R group being a hydrogen atom.

Stereochemistry of Amino Acids

The spatial arrangement of atoms around the α-carbon gives rise to stereoisomerism in amino acids. Most amino acids are chiral, meaning they exist in two mirror-image forms (enantiomers).

Chirality: When four different groups are attached to the α-carbon, it is a chiral center.
Enantiomers: L- and D- forms; proteins are composed almost exclusively of L-amino acids.
Glycine: The only non-chiral amino acid, as its R group is hydrogen.
Fischer Projection: A 2D representation used to depict stereochemistry.

Example: L-alanine and D-alanine are enantiomers, with L-alanine being the form found in proteins.

Classification of Naturally Occurring Amino Acids

The 20 common amino acids found in proteins are classified based on the properties of their side chains.

Nonpolar Aliphatic: Glycine, Alanine, Valine, Leucine, Isoleucine
Nonpolar Aromatic: Phenylalanine, Tyrosine, Tryptophan
Polar Uncharged: Serine, Threonine, Asparagine, Glutamine, Cysteine
Positively Charged (Basic): Lysine, Arginine, Histidine
Negatively Charged (Acidic): Aspartic acid, Glutamic acid

Example: Tyrosine and tryptophan are aromatic amino acids that absorb UV light.

General Properties of Amino Acids

Amino acids exhibit distinct chemical properties, including UV absorbance, ionization, and posttranslational modifications.

UV Absorption: Aromatic amino acids (tyrosine, tryptophan) absorb at 280 nm; nucleic acids absorb at 260 nm.
pKa Values: Each ionizable group has a characteristic pKa value, affecting its charge at different pH levels.
Titration Curve: Shows how the charge of an amino acid (e.g., histidine) changes with pH; the isoelectric point (pI) is where net charge is zero.
Posttranslational Modifications: Chemical changes after protein synthesis, such as phosphorylation, hydroxylation, acetylation, and carboxylation, which affect function and regulation.

Example: Phosphorylation of serine residues is important in cell signaling.

Group Type	Typical pKa	Range
α-Carboxyl	3.5–4.0	3.5–4.0
Side-chain carboxyl (Asp, Glu)	4.0–4.8	4.0–4.8
Imidazole (His)	6.5–7.4	6.5–7.4
Cysteine (–SH)	8.5–10.5	8.5–10.5
Phenolic (Tyr)	8.0–9.0	8.0–9.0
Side-chain amino (Lys)	9.8–10.4	9.8–10.4
Guanidino (Arg)	~12	~12

5.2 Peptides and the Peptide Bond

Peptide Bond Formation between Amino Acids

Peptide bonds link amino acids together to form peptides and proteins. This process involves a condensation reaction, releasing water and forming a covalent bond between the carboxyl group of one amino acid and the amino group of another.

Condensation Reaction: Two amino acids join, releasing H2O.
Energetics: The reaction is not thermodynamically favorable and is coupled to ATP hydrolysis during protein biosynthesis.

Equation:

Structure of the Peptide Bond

The peptide bond is characterized by electron delocalization, which imparts planarity and stability to the bond. This restricts rotation and contributes to the overall structure of proteins.

Planar and Stable: Due to resonance, the peptide bond is rigid and planar.
Partial Double Bond Character: Limits rotation around the bond.

Peptide Bond Cleavage

Peptide bonds can be hydrolyzed under specific conditions, such as strong acid, high temperature, or by enzymatic catalysis. Proteases are enzymes that cleave peptide bonds at specific sites.

Hydrolysis: for peptide bond hydrolysis is about –10 kJ/mol.
Stability: Peptides are stable unless exposed to strong acid, high temperature, or a catalyst.
Proteases: Enzymes that cleave specific peptide bonds, often with sequence specificity.

Enzyme	Preferred Site	Source
Trypsin	R1 = Lys, Arg	Digestive system of animals
Chymotrypsin	R1 = Tyr, Trp, Phe, Leu	Digestive system of animals
Thrombin	R1 = Arg	Blood, vertebrates
V-8 endopeptidase	R1 = Asp, Glu	Staphylococcus aureus
Thermolysin	R2 = Ile, Met, Phe, Val	Bacillus thermoproteolyticus
Cyanogen bromide	R1 = Met	Chemical reagent

Oligopeptides and Polypeptides

Peptides are short chains of amino acids, while polypeptides are longer chains that can fold into functional proteins.

Oligopeptides: Chains of 3–15 amino acid residues.
Polypeptides: Chains containing more than 15 residues.

Example: A tetrapeptide consists of four amino acids linked by peptide bonds.

Important Peptide Regions

Peptides and proteins have distinct regions, including the amino (N-) terminus, carboxy (C-) terminus, main chain, and side chains. These regions are critical for protein structure and function.

N-terminus: The end with a free amino group.
C-terminus: The end with a free carboxyl group.
Main Chain: The repeating backbone of the peptide.
Side Chains: The variable R groups projecting from the backbone.

Common Modifications of Amino- and Carboxy-Termini in Peptides

Peptide termini can be chemically modified, affecting stability, localization, and function.

N-formyl group: Blocks the N-terminus.
N-acetyl group: Blocks the N-terminus, common in eukaryotic proteins.
C-terminal amide: Blocks the C-terminus.

Peptides and Proteins as Polyampholytes

Peptides and proteins contain multiple ionizable groups, allowing them to act as polyampholytes—molecules with both acidic and basic groups. Their net charge varies with pH.

Ionization Behavior: As pH increases, the overall charge becomes more negative; as pH decreases, it becomes more positive.
Isoelectric Point (pI): The pH at which the net charge is zero.

Example: The titration curve of a tetrapeptide shows stepwise changes in charge as pH changes.

Additional info: The notes provide foundational knowledge for understanding protein structure and function, including the chemical basis for amino acid diversity, peptide bond formation, and the role of modifications in protein biology.