--- title: "Amino Acids and Peptides: Zwitterions and the Peptide Bond" description: "Amino acids contain acidic and basic groups whose protonation changes with pH. Ionisable side chains can add charge, so the whole molecule need not be neutral near pH 7. Peptide bonds join residues th" canonical: https://lightmysky.com/learn/science/amino-acids-and-peptides-zwitterions-and-the-peptide-bond-mt_cXdg1yjq-n source: https://lightmysky.com/learn/science/amino-acids-and-peptides-zwitterions-and-the-peptide-bond-mt_cXdg1yjq-n.md retrieved: 2026-11-12 --- > **Agent view.** This is the Markdown twin of the page, for tools and assistants. > When to use this site, and the call that answers each job: https://lightmysky.com/agent-instructions.md > API description (OpenAPI 3.1): https://lightmysky.com/openapi.json · Authentication: https://lightmysky.com/auth.md > Pricing: https://lightmysky.com/pricing.md · Catalog: https://lightmysky.com/llms.txt · Full catalog: https://lightmysky.com/llms-full.txt > Every machine-readable file on this domain: https://lightmysky.com/.well-known/ai-catalog.json > Ask for Markdown with `Accept: text/markdown`, a `.md` address, or `?mode=agent`. # Amino Acids and Peptides: Zwitterions and the Peptide Bond Amino acids contain acidic and basic groups whose protonation changes with pH. Ionisable side chains can add charge, so the whole molecule need not be neutral near pH 7. Peptide bonds join residues through nearly planar amide groups with restricted rotation. Subject: Science · Area: Chemistry · Ages 21 to 22 Page: https://lightmysky.com/learn/science/amino-acids-and-peptides-zwitterions-and-the-peptide-bond-mt_cXdg1yjq-n ## Ready when they can - Draws the dominant form of an amino acid at a stated pH and calculates its isoelectric point from the pKa values - Explains why the peptide bond is planar using delocalisation and predicts the preferred geometry - Explains why peptide synthesis needs both activation and protection, and where each is applied - Predicts the direction an amino acid moves during electrophoresis at a given pH ## Lesson: Charged ends and stiff links Protein amino acids have an alpha carbon bonded to an amino nitrogen, carboxyl group, hydrogen and side chain. Proline's side chain also bonds to its nitrogen, forming a ring. Near pH 7, alanine mainly has NH3+ and COO- groups, with net charge zero. This form is a zwitterion. Solution equilibria set protonation; a direct internal proton transfer is not required. Ionisable side chains can give other amino acids a nonzero net charge. Compare pH with each ionisable group's pKa. Below its pKa, the protonated form is favoured; above it, the deprotonated form is favoured. Far below both alanine pKa values, NH3+ and COOH give net charge +1. Far above both, NH2 and COO- give -1. Near a pKa, substantial amounts of both forms occur. Include any ionisable side chain in the charge sum. *(drawing: Increasing pH removes protons. These cells show group states and net charges, not a molecular structure.)* The isoelectric point, pI, is the pH where average net charge is zero. In the usual simple amino-acid model, estimate pI by averaging the two pKa values surrounding the zero-charge form. Track charges to choose the pair, including side chains. For illustrative values 2.1, 4.1 and 9.6 with successive charges +1, 0, -1 and -2, use 2.1 and 4.1: pI is about (2.1 + 4.1) / 2 = 3.1. For glutamic acid, use illustrative pKa values 2.2 (alpha COOH), 4.3 (side-chain COOH) and 9.7 (NH3+). Compare pH with each pKa: above favours deprotonation; below favours protonation. At pH 7, the main form is NH3+-CH(COO-)-CH2-CH2-COO-. Its charges give +1 - 1 - 1 = -1, so it drifts toward the positive anode. The zero-charge form lies between the two carboxyl dissociations; pI is about 3.25. In electrophoresis, free amino acids drift according to average charge, without requiring their oxidation or reduction. Positive charge gives drift toward the negative cathode; negative charge gives drift toward the positive anode. Below pI average charge is positive; above pI it is negative. Glutamic acid at pH 7 therefore drifts toward the anode. At pI there is no net electrophoretic drift, though diffusion and fluid motion can still move molecules. A peptide bond joins one residue's carboxyl carbon to the next residue's amino nitrogen. Nitrogen's lone pair delocalises with the carbonyl, giving the C-N bond partial double-bond character. The peptide unit is nearly planar, and C-N rotation is restricted, not impossible. Most peptide bonds favour trans because it reduces steric crowding. Bonds immediately before proline have a larger cis fraction than other peptide bonds. A free carboxylic acid and amine often form an ammonium carboxylate salt rather than a peptide. For controlled laboratory coupling, activate the carboxyl group, for example as an activated ester, to aid amine attack. Protect groups that could react at unwanted sites, leaving the intended pair available. Coupling forms the amide. Remove selected protecting groups when needed; some remain through several couplings. *(drawing: This is a planning sequence, not a universal reaction schedule. Deprotection depends on the next synthesis step.)* **Recap.** Use pH and pKa to track charge and estimate pI. Charge sets electrophoretic drift. Delocalisation restricts peptide rotation; activation and protection control coupling. *Lesson, questions and flashcards written for this dataset.* ## Practice 8 questions on this page, each with its working shown. ## Needs first - [Amines and Amides: Basicity and the Nitrogen Functional Groups](https://lightmysky.com/learn/science/amines-and-amides-basicity-and-the-nitrogen-functional-groups-mt_cGP3ZJ8S6h) ## Optional connections - [Protein Structure from Primary to Quaternary](https://lightmysky.com/learn/science/protein-structure-from-primary-to-quaternary-mt_bMdQS2lqSI) - [pKa as a Predictive Tool in Organic Chemistry](https://lightmysky.com/learn/science/pka-as-a-predictive-tool-in-organic-chemistry-mt_fI03mNIC_m) ## Opens up - [Ion Exchange and Electrophoretic Separations](https://lightmysky.com/learn/science/ion-exchange-and-electrophoretic-separations-mt_6xaiivXbAd) - [Chemical Biology: Bioconjugation and Reporting on a Molecule in a Cell](https://lightmysky.com/learn/science/chemical-biology-bioconjugation-and-reporting-on-a-molecule-in-a-cell-mt_nsNwVhPRFN)