Chapter 1 — Exercises

How to use these. Items marked † have worked solutions in Appendix M. The rest are deliberately open — in a book about weighing evidence, an answer key that pretended every question had one right answer would teach the opposite of the lesson.

Work them in order. The recall items are fast; the later ones are where the skill is built.

A. Recall and comprehension

1.1 Draw or describe the general structure of an amino acid. Label the four groups attached to the alpha carbon and state which one differs between the twenty.

1.2 † A peptide bond forms between which two functional groups? What small molecule is released, and what is the reverse reaction called?

1.3 Define residue. Why is that word used instead of "amino acid" once a chain has formed?

1.4 Which end of a peptide chain is numbered position 1, and why does getting this backwards matter?

1.5 † State the conventional size boundary between a peptide and a protein, then explain in one sentence why it is a convention rather than a chemical distinction.

1.6 Name the two principal secondary structures and state what kind of bond holds each together.

1.7 What is a disulfide bond, which amino acid forms it, and name one drug in this book that depends on them.

1.8 † Why does proline disrupt an alpha helix?

1.9 Approximately how many daltons are: aspirin, insulin, a therapeutic monoclonal antibody?

1.10 Give the three-letter and one-letter codes for any five amino acids, and state which family each belongs to.

B. Applied reasoning

1.11 † A product is advertised as an "oral peptide spray, absorbed sublingually for maximum bioavailability." Using only Chapter 1, list three specific questions you would want answered before taking that claim seriously. For each, say what a satisfactory answer would look like.

1.12 A peptide has the sequence GEPPPGKPADDAGLV. Without consulting any other source, state: (a) its length; (b) how many prolines it contains and what that implies structurally; (c) whether it carries net positive or negative charge at body pH, and how you can tell; (d) which residue would most likely be used as an attachment point for chemical modification.

1.13 Two peptides have identical amino acid composition but different sequences. Are they the same molecule? Explain using the levels of structure.

1.14 † A manufacturer's synthesis process occasionally omits a single residue from a 30-residue peptide, producing a 29-residue product. Argue both sides: why might this matter enormously, and under what circumstances might it not matter at all? What would you need to know to decide?

1.15 Explain why peptide drugs generally target receptors on the outside of cells rather than molecules inside them, and name one consequence of that limitation for drug development.

1.16 Insulin is stored as a zinc-coordinated hexamer and must dissociate into single molecules before it can act. Which level of structure is that, and why would an engineer want to make a version that dissociates faster?

C. "Explain this to a friend"

These are the items that prove you understood. Write for someone with no science background. No jargon unless you define it in the same sentence.

1.17 † In four sentences or fewer, explain what a peptide is to someone who has heard of Ozempic and nothing else.

1.18 Your friend says: "Peptides are natural, so they're safer than drugs." Respond in a way that is (a) accurate, (b) not condescending, and (c) concedes what is genuinely true in their claim before addressing what is not.

1.19 Explain, without using the words hydrolysis, protease, or bioavailability, why most peptide medicines have to be injected.

1.20 † A relative is about to spend \$120 on an oral collagen peptide supplement and asks what you think. Write what you would actually say — including honestly flagging the part of the question you cannot settle from chemistry alone.

D. "Identify the red flags"

1.21 A website sells a compound and states: "Our peptide is 99% pure, third-party tested, and identical to the peptide used in clinical research." Identify at least four distinct things this sentence does not establish. (You will get the full treatment in Chapter 34; do what you can now.)

1.22 † A product page describes its active ingredient only as "a proprietary peptide complex." List what information is missing that Field 1 of the Evidence Dossier would require, and state what the omission itself suggests.

1.23 A supplement is marketed as containing "bioidentical human growth hormone peptides, orally active." Using Chapter 1 alone, identify the two claims in that phrase that are in tension with each other.

E. Naming and nomenclature

1.24 For each of the following, state the likely class from the name alone: dulaglutide, degarelix, somatropin, erenumab, sermorelin, linaclotide.

1.25 † Explain the difference between a compound named -relin and one named -relix, and give a clinical situation in which that difference has a real consequence.

1.26 Ozempic, Wegovy, and Rybelsus contain the same active molecule. Explain what actually differs between them, and why a patient might be approved for one and denied another.

1.27 BPC-157, TB-500, CJC-1295, and MK-677 are all known by laboratory codes rather than generic names. What does that pattern suggest about their regulatory histories? What does it not prove?

F. Structure and inference

1.28 † Oxytocin and vasopressin are both nine residues and differ at two positions, yet produce substantially different physiology. Using the levels of structure, explain how a two-residue difference can produce that much functional divergence. Then state what this implies about the reliability of a synthesis process.

1.29 A peptide is described as "largely random coil in solution." Does that mean it has no shape? Explain what it means and why it complicates predicting the molecule's behavior from sequence.

1.30 Rank by expected duration in the bloodstream, longest to shortest, and justify your ranking using only Chapter 1 concepts: native GLP-1; semaglutide; a therapeutic antibody; aspirin.

G. Judgment and ethics

1.31 A cosmetic company names an ingredient "acetyl hexapeptide-8." Chemically, the name tells you a modification and a length. Is naming it this way misleading, informative, both, or neither? Argue a position.

1.32 † Someone argues: "The category 'peptide' is meaningless for evaluating whether something works, so we should stop using the word." Argue against this position — identify what the category genuinely does tell you and where it earns its keep.

1.33 A friend who is already injecting a gray-market peptide asks your opinion. You have read only Chapter 1. Write what you would say — including an honest statement of what you do not yet know. Then write what you would say if you wanted to end the conversation and lose the friendship, and compare them. What is the difference actually made of?

H. Evidence Dossier extension

1.34 † Complete Field 1 (Identity) for all 5–10 peptides you selected in the chapter checkpoint. For each, note explicitly whether a full sequence is publicly available. Then answer: did any of your chosen peptides turn out to be difficult to pin down, and what does that difficulty suggest?

1.35 For each peptide in your dossier, write your one-sentence prior belief and a confidence score from 1 to 10. Date it. Seal it — literally, if that helps — and do not revise it. Chapter 40 will ask for it.

1.36 Look at your dossier's confidence scores. Are they higher for compounds you hoped would work? Write one honest paragraph about what you notice. There is no wrong answer here and no answer key; the exercise is the noticing.