Chapter 1 — Quiz

Twenty-four self-check questions. Answers in the collapsed block at the bottom — write yours down first, because recognizing an answer and producing one are different skills, and only one of them survives a conversation.

Multiple choice

1. The part of an amino acid that differs between the twenty is the: a) amino group b) carboxyl group c) R group (side chain) d) alpha carbon

2. A peptide bond forms with the release of: a) carbon dioxide b) water c) ammonia d) a hydrogen ion

3. Peptide sequences are conventionally written and numbered starting from the: a) C-terminus b) N-terminus c) largest residue d) first charged residue

4. Which amino acid forms disulfide bonds? a) proline b) glycine c) lysine d) cysteine

5. Which amino acid is most often used as an attachment point for chemical modification? a) lysine b) proline c) valine d) aspartate

6. Approximately how many amino acids are in native GLP-1? a) 9 b) 15 c) 30 d) 51

7. Insulin consists of: a) one chain of 51 residues b) two chains, 21 and 30 residues, disulfide-linked c) three chains of 17 residues d) one chain of 191 residues

8. The conventional boundary between "peptide" and "protein" is approximately: a) 20 residues b) 50 residues c) 100 residues d) there is a precise chemical boundary at 51

9. An alpha helix contains approximately how many residues per turn? a) 2.0 b) 3.6 c) 5.5 d) 10

10. Proline disrupts alpha helices because: a) it is too large b) it carries a charge c) its side chain bonds back to the backbone nitrogen, preventing the required hydrogen bonding d) it forms disulfide bonds

11. Most peptide drugs must be injected because: a) they are too expensive to formulate as tablets b) digestive proteases break peptide bonds and the intact molecules are poorly absorbed c) regulators require it d) they are unstable at room temperature

12. Oral semaglutide achieves bioavailability of approximately: a) 1% b) 15% c) 50% d) 90%

13. The drug name stem "-tide" indicates: a) a monoclonal antibody b) a peptide c) a steroid d) an enzyme inhibitor

14. "-relin" and "-relix" differ in that: a) one is oral and one is injected b) one stimulates a releasing-hormone receptor, the other blocks it c) one is human and one is synthetic d) they are interchangeable

15. A therapeutic monoclonal antibody such as trastuzumab has a molecular weight of approximately: a) 1,400 Da b) 5,800 Da c) 22,000 Da d) 148,000 Da

16. Which is NOT a genuine advantage of peptides over small molecules as drugs? a) high target selectivity b) potency at very low concentrations c) ability to reach intracellular targets d) breakdown into ordinary amino acids

Short answer

17. In one sentence each, define primary, secondary, and tertiary structure.

18. Explain why the reversibility of the peptide bond is the central fact of peptide pharmacology.

19. A compound has been known only by a laboratory code for over two decades. What does that suggest, and what does it fail to prove?

20. Semaglutide differs from human GLP-1 at two positions and carries an added fatty acid chain. Why does this undermine the claim that "peptide drugs are just the natural molecule"?

21. Give two distinct reasons why "peptides are natural, so they're safe" is not a sound argument.

22. Explain what it means for a peptide to be "largely random coil in solution," and why that complicates predicting its function from sequence alone.

Applying the rating discipline

These four items test the skill the rest of the book runs on. Chapter 1 issues no ratings — but it establishes why.

23. Chapter 1 deliberately issues no evidence ratings. Explain why, in terms of what a rating attaches to.

24. A source states: "BPC-157: rating ❌." Chapter 1 has given you enough to say what is wrong with that formulation, even before you know anything about BPC-157's evidence. What is missing?

Answer key **1.** c — the R group. The amino group, carboxyl group, and hydrogen are identical in all twenty. **2.** b — water. It is a condensation reaction; the reverse, hydrolysis, adds water back and is what your digestive proteases do. **3.** b — the N-terminus. Reading a sequence backwards describes a different molecule. **4.** d — cysteine. Its sulfur-containing side chain links to another cysteine's. **5.** a — lysine, whose side chain terminates in a free amino group that can be modified without disturbing the rest of the molecule. **6.** c — 30 amino acids. **7.** b — two chains (A = 21, B = 30) joined by disulfide bonds, ~5,800 Da total. **8.** b — approximately 50 residues, and it is a convention. There is no chemical change at residue 51; different sources draw the line at 30, 40, or 100. **9.** b — about 3.6 residues per turn, with hydrogen bonds running from each residue to the one four positions along. **10.** c — proline's side chain loops back to the backbone nitrogen, preventing the hydrogen bonding pattern a helix requires. **11.** b — proteolysis in the stomach and small intestine, compounded by poor absorption of intact peptides across the intestinal wall. **12.** a — roughly 1%, which is why the tablet contains far more drug than the injection and must be taken on an empty stomach with a waiting period. **13.** b — a peptide. **14.** b — `-relin` stimulates, `-relix` blocks. In prostate cancer this is the difference between an initial testosterone surge before suppression and immediate suppression. **15.** d — about 148,000 Da, roughly thirty times the mass of a mid-sized peptide. **16.** c — peptides generally *cannot* reach intracellular targets. That is a limitation, not an advantage; it is one of the main reasons small molecules remain dominant. **17.** *Primary* — the amino acid sequence. *Secondary* — local regular folding of the backbone (alpha helices, beta sheets) held by hydrogen bonds. *Tertiary* — the overall three-dimensional arrangement of the folded chain. **18.** Because the same bond that builds a peptide is the bond your body is specialized to destroy. Proteases and peptidases hydrolyze peptide bonds continuously — that is how you digest protein — which means every peptide drug is fundamentally an answer to the question of how to survive that. Half-life, route of administration, chemical modification, and cost all follow from it. **19.** Generic names are assigned when a compound enters serious clinical development. A compound still known only by a laboratory code decades later almost certainly never completed that process. It does *not* prove the compound does nothing, is unsafe, or was rejected — a molecule can go undeveloped because it is unpatentable, because a company folded, or because nobody funded it. It is strong evidence about regulatory history and no evidence about pharmacology. **20.** Because the modifications are the entire point. The position-8 substitution exists specifically so the enzyme DPP-4 cannot recognize the molecule; the fatty acid chain exists so it binds albumin and persists for a week. A drug engineered to evade the body's normal handling is precisely not the molecule the body already knows what to do with. **21.** Any two of: (a) natural provenance predicts nothing about safety — botulinum toxin and ricin are natural; (b) most peptide drugs are deliberately *not* the natural molecule; (c) endogenous peptides arrive in regulated pulses at specific tissues and are terminated on cue, while an injection is a flat sustained whole-body exposure no physiology produces; (d) the actual documented harms in the unregulated market come from contamination, wrong identity, and wrong concentration — none of which "natural" addresses. **22.** It means the peptide has no single stable shape in water and may only fold when it encounters its receptor or a membrane. The shape is a property of the molecule *plus its target* rather than of the molecule alone — which is why predicting a short peptide's behavior from sequence is much harder than the equivalent problem for a large, stably folded protein. **23.** Because a rating attaches to a **claim**, not to a molecule — a specific claim, for a specific population, on a specific endpoint. Chapter 1 makes no claims about what any peptide does, so there is nothing to rate. Chapter 5 introduces the machinery. **24.** It has no claim attached. "BPC-157: ❌" states a verdict without saying ❌ *for what, in whom, measured how*. The molecule has different evidentiary situations for tendon healing in humans, for gut protection in rodents, and for safety — and compressing all of them into one symbol destroys exactly the information a reader needs. A correct formulation names the claim, the population, the endpoint, the reason, and what would change it.