chapter 5 section 5

Question 1

Why is chemical synthesis of peptides challenging?

Answer 1

Side chains may react undesirably

Question 2

What is the main advantage of laboratory peptide synthesis?

Answer 2

: It allows creation of polypeptides with any desired sequence to study structure–function relationships.

Question 3

What is the purpose of chemical peptide synthesis in the lab?

Answer 3

To create polypeptides of any desired sequence for studying structure–function relationships.

Question 4

Why is making a specific peptide sequence challenging?

Answer 4

Side-chain functional groups can react undesirably during peptide bond formation.

Question 5

How is correct sequence ensured during synthesis?

Answer 5

Protecting groups block reactive functional groups and are removed after peptide bonds form.

Question 6

What must be true about protecting groups?

Answer 6

They must be removable under conditions that do not break the newly formed peptide bonds.

Question 7

What is the first step in SPPS?

Answer 7

Attach the C-terminal amino acid to an insoluble resin

Question 8

What is the role of Fmoc in SPPS?

Answer 8

Fmoc protects the α-amino group and is removed under basic conditions without affecting the peptide–resin linkage.

Question 9

How is the carboxyl group of incoming amino acids activated?

Answer 9

Using DIPCDI (N,N′-diisopropylcarbodiimide) to form a peptide bond with the growing chain.

Question 10

What happens after peptide bond formation in each cycle?

Answer 10

The N-terminal Fmoc group is removed with a base (e.g., piperidine) to expose the next amino group for elongation.

Question 11

How are side-chain functional groups protected?

Answer 11

With acid-labile tertiary butyl (tBu) groups as orthogonal protecting groups.

Question 12

How is the completed peptide released from the resin?

Answer 12

Treatment with HF, which also removes tBu side-chain protecting groups.

Question 13

Why is SPPS advantageous?

Answer 13

It allows stepwise, controlled synthesis of peptides of defined sequence while easily isolating intermediates via insoluble resin.

Question 14

Who pioneered solid-phase peptide synthesis?

Answer 14

Bruce Merrifield.

Question 15

What is the key feature of solid-phase peptide synthesis?

Answer 15

Peptides are anchored by their C-terminal residue to an insoluble resin, allowing easy recovery by filtration.

Question 16

How are new amino acids added in SPPS?

Answer 16

Successively at the free N-terminal of the growing peptide chain.

Question 17

Why is SPPS advantageous for peptide synthesis?

Answer 17

It simplifies purification of intermediates and allows automation of the cyclic synthesis process.

Question 18

How is SPPS typically automated?

Answer 18

Reagents are pumped in and removed in a programmed cycle within a small reaction vessel.