Chapter 4 section 2

Question 1

How does the α-amino group affect the α-carboxyl group’s acidity?

Answer 1

It makes the α-COOH more acidic (lowers its pKa)

Question 2

What is the typical pKa of the α-carboxyl group in amino acids?

Answer 2

2.0–2.1

Question 3

Why does the α-NH₃⁺ group lower the pKa of α-COOH?

Answer 3

Because the positively charged ammonium group pulls electrons away, it stabilizes the carboxylate, making the α-COOH more acidic

Question 4

Does the α-COO⁻ group affect the α-amino group?

Answer 4

Yes, it influences the pKa of α-NH₃⁺

Question 5

How many unnatural amino acids (UAAs) have been incorporated into proteins using Schultz’s methodology?

Answer 5

Over 160

Question 6

In which organisms can UAAs be incorporated?

Answer 6

E. coli, yeast, mammalian cells

Question 7

What is the purpose of incorporating UAAs at unique protein sites?

Answer 7

To study protein structure/function and introduce new catalytic functions

Question 8

What new functions can designer enzymes created with UAAs perform?

Answer 8

Catalysis, metal-dependent reactions, potential therapeutic applications

Question 9

Name some applications of UAAs in biotechnology and medicine.

Answer 9

Novel antibodies, immunotoxins, vaccines, medical imaging probes

Question 10

What is the main source of protein diversity in nature?

Answer 10

The 20 common amino acids

Question 11

how can protein function be expanded beyond the common 20 amino acids?

Answer 11

By creating and incorporating unnatural amino acids (UAAs)

Question 12

how many UAAs have been incorporated using Schultz’s methodology?

Answer 12

Over 160

Question 13

In which organisms can UAAs be incorporated into proteins?

Answer 13

E. coli, yeast, mammalian cells

Question 14

What applications do UAAs enable in biotechnology and medicine?

Answer 14

Designer enzymes, novel antibodies, immunotoxins, vaccines, medical imaging probes

Question 15

What is the general strategy of UAA methodology?

Answer 15

Introduce novel chemical functionalities at unique protein sites to alter structure and function

Question 16

What enables proteins to have vast structural and functional diversity in nature?

Answer 16

The 20 common amino acids

Question 17

How can protein function be expanded beyond natural amino acids?

Answer 17

by incorporating unnatural amino acids (UAAs)

Question 18

How many UAAs have been successfully incorporated using Schultz’s methodology?

Answer 18

Over 160

Question 19

In which organisms have UAAs been incorporated?

Answer 19

E. coli, yeast, and mammalian cells

Question 20

What is the purpose of incorporating UAAs at specific protein sites?

Answer 20

To introduce new chemical functionalities and study protein structure/function

Question 21

What therapeutic and biotechnological applications are enabled by UAAs?

Answer 21

Designer enzymes, antibodies, immunotoxins, vaccines, and medical imaging probes

Question 22

What is the general strategy behind UAA methodology?

Answer 22

insert novel chemical functionalities at unique protein sites to expand protein chemistry

Question 23

What type of acids are the common amino acids chemically?

Answer 23

Weak polyprotic acids

Question 24

What does “polyprotic” mean in this context?

Answer 24

They have more than one ionizable hydrogen

Question 25

Which amino acid is used as a simple example for acid–base behavior?

Answer 25

Glycine

Question 26

What is the state of glycine at low pH?

Answer 26

Both amino and carboxyl groups are protonated; net positive charge (Gly⁺)

Question 27

What is glycine hydrochloride?

Answer 27

Glycine in its fully protonated form with chloride as the counterion

Question 28

What is a typical shift in side-chain pKa values when amino acids are in proteins?

Answer 28

About 1 pH unit closer to neutrality.

Question 29

Why is understanding protein-specific pKa important?

Answer 29

It helps predict the charge state and function of amino acids in the protein.

Question 30

Which amino acid side chains contain additional carboxyl groups?

Answer 30

Aspartic acid (β-carboxyl) and glutamic acid (γ-carboxyl).

Question 31

Which amino acid side chains contain additional amino groups?

Answer 31

Lysine (ε-amino).

Question 32

Which amino acid has an ionizable imidazolium group?

Answer 32

Histidine.

Question 33

Which amino acid contains a guanidinium group?

Answer 33

Arginine.

Question 34

How do side-chain pKa values compare to α-group pKa values?

Answer 34

Side-chain pKa values are intermediate—slightly diminished effect from α-carbon groups.

Question 35

Why are glutamic acid and aspartic acid side-chain carboxyl pKa values lower than typical aliphatic carboxyls?

Answer 35

The α-amino group exerts an electron-withdrawing effect, lowering pKa.

Question 36

Why is lysine’s ε-amino pKa higher than its α-amino pKa?

Answer 36

It is several carbons removed from the α-carbon, so the electron-withdrawing effect is weaker.

Question 37

How can the pKa of amino acid side chains in proteins differ from free amino acids?

Answer 37

Side-chain pKa values in proteins are on average ~1 pH unit closer to neutrality and can be dramatically altered by the local chemical environment.