Amino Acids and Peptides

The isoelectric point (π) is the pH at which an amino acid carries no net charge (the zwitterion form dominates). For a simple neutral amino acid like alanine (side chain is just an alkyl group, no extra acid or base site), the π sits near the average of the α-amino and α-carboxyl pKa values, roughly in the middle of the pH scale. An amino acid with a basic side chain, like arginine (guanidinium group, strongly basic), needs a HIGHER pH before that extra positively-charged group loses its proton, so its π is shifted well above alanine's. An amino acid with an acidic side chain, like glutamic acid (a second carboxylic acid group), becomes net-neutral at a LOWER pH than alanine, because the extra acidic group needs to be at least partly deprotonated already for the molecule to reach neutrality. This gives the general ordering: basic-side-chain amino acid > neutral amino acid > acidic-side-chain amino acid, i.e. Arg > Ala > Glu, and the same reasoning extends to ranking any other set of amino acids once you classify each side chain as acidic, basic or neutral.

Joining amino acid monomers into a linear peptide chain forms one peptide bond, and loses one water molecule, at each junction between consecutive residues. Linking n copies of the same amino acid therefore loses exactly (n-1) molecules of water from n times the monomer formula. For glycine (C₂H₅NO₂) joined into a linear chain of 10 residues: start from 10 x C₂H₅NO₂ = C₂₀H₅₀N₁₀O₂₀, then subtract 9 x H₂O (nine junctions between ten residues) = subtract H₁₈O₉, giving a final formula of C₂₀H₃₂N₁₀O₁₁. Apply the same (n-1)-waters-lost logic to any oligomerisation-by-condensation stoichiometry question, whether the monomers are identical (as here) or different amino acids in a defined sequence.

When two different amino acids (say A and B) are combined pairwise into dipeptides, sequence matters — a peptide bond is directional (it has a distinct N-terminus and C-terminus), so A-B and B-A are two DIFFERENT dipeptides, not the same one counted twice. With two amino acids, this gives four possible dipeptides in total: A-A, B-B, A-B and B-A. Whether each one is optically active depends on how many genuine stereocentres survive in the final dipeptide: glycine itself has NO stereocentre (its side chain is just a hydrogen), so any dipeptide built entirely from glycine (Gly-Gly) has zero stereocentres and is optically INACTIVE; every other combination that includes at least one amino acid with a genuine side chain (like valine, which does have a stereocentre) retains at least one stereocentre in the dipeptide and is optically active. For a glycine + valine mixture, this means Gly-Gly is the one inactive dipeptide, and the other three (Val-Val, Gly-Val, Val-Gly) are all optically active — four dipeptides total, three of them optically active.

In any peptide, count peptide bonds as one fewer than the number of residues (a tripeptide has exactly two peptide bonds, linking residue 1 to 2 and residue 2 to 3). Count chiral centres residue by residue: a residue contributes a chiral α-carbon only if its side chain (R group) is not simply hydrogen — alanine (R = CH₃) and phenylalanine (R = CH₂Ph) each contribute one chiral centre, while glycine (R = H) contributes none, since its α-carbon then carries two identical hydrogens and is not a stereocentre. A tripeptide built from alanine, phenylalanine and glycine therefore has exactly 2 chiral centres (from Ala and Phe, not Gly) and 2 peptide bonds — read any peptide structure this same way, residue by residue, rather than trying to count stereocentres from the overall molecular formula.

Titrating the fully protonated amino acid (NH₃+-CHR-COOH) with NaOH removes its two acidic protons in turn, so the curve has two buffer regions separated by one steep step. In the first buffer region the carboxyl group is losing its proton: halfway through it (about 25% of the total NaOH needed) [NH₃+-CHR-COOH] = [NH₃+-CHR-COO⁻], so the pH equals pKa₁. The steep rise at 50% marks the first equivalence point, where the molecule is entirely the zwitterion NH₃+-CHR-COO⁻, the isoelectric point. In the second buffer region the NH₃⁺ group loses its proton: at about 75%, [NH₂-CHR-COO⁻] = [NH₃+-CHR-COO⁻], so the pH equals pKa₂. The zwitterion is also the form that dominates in plain water. Classify each labelled point as halfway through a buffer region or as an equivalence point before you read any of the statements.