pH/pKa- Amino Acids

Question 1

Pharmaceutical compounds taken orally can be absorbed in the stomach (very acidic pH), in the upper intestine (acidic pH) or the lower intestine (neutral to basic pH). Ambucetamide (see structure in ppt slide 5) has been used as an antispasmodic drug. It has a pKa of 8.4 for the ionization of the amino group. Where would you predict this drug would be most efficiently absorbed?

Answer 1

Lower intestine (because it will likely be deprotonated and neutral at the more basic pH and uncharged things absorb)

Question 2

_____ particles are not easily absorbed.

Answer 2

Charged

Question 3

Given the amino acid alanine (pictured in slide 7), what is the name of the group 2 (H2N-)?

Answer 3

amino group

Question 4

Given the amino acid alanine (pictured in slide 7), which group of the Ala molecule would be different if this was a different amino acid?

Answer 4

Group 3 (the R group which is -CH3 here)

Question 5

Given the amino acid alanine (pictured in slide 7), if the Ala was in the middle of a peptide chain, which part(s) would be bonded to a neighboring amino acid?

Answer 5

Groups 1 and 2 (the carboxyl and amino groups respectively)

Question 6

Given the amino acid alanine (pictured at slide 9), what groups would be ionized at pH 1.0? What is the charge?

Answer 6

Group 2 (amino group); positive (pH is low, so amino group (high pKa) is protonated and acquires +1 charge)

Question 7

Given the amino acid alanine (pictured at slide 9), what groups would be ionized at pH 12.0? What is the charge?

Answer 7

Group 1 (carboxyl group); negative charge (pH is high so carboxyl group (low pKa) is deprotonated and acquires -1 charge)

Question 8

What is the charge of the N-terminus at pH 1 (Refer to the structure on slide 11)?

Answer 8

Positive

Question 9

What is the charge of the C-terminus at a pH of 1 (Refer to the structure on slide 11)?

Answer 9

Neutral

Question 10

What is the charge of the lysine at a pH of 1 (Refer to the structure on slide 11)?

Answer 10

Positive

Question 11

What is the charge of the histidine at a pH of 1 (Refer to the structure on slide 11)?

Answer 11

Positive (note that the nitrogen opposite the NH in the ring indicated with the yellow arrow accepts the proton and acquires a positive charge)

Question 12

An acid is _____ when pH is less than pKa.

Answer 12

protonated

Question 13

An acid is ______ when pH is greater than pKa.

Answer 13

deprotonated

Question 14

You are designing a new therapeutic antibody that interacts with the surface of cell membranes. In order to promote endocytosis of the antibody at physiological pH, which amino acid should be used throughout the antibody’s structure?

Answer 14

Lysine (pI=9.74) because cell membranes are negatively charged, so the antibody must be positively charged at physiological pH (7.4) in order to be endocytosed by the cell, so the pI of the antibody must be greater than 7.4 to ensure that most of the antibody molecules are in a positively charged state