Question

(a) Draw the structure of the peptide “SMELLY” at physiological pH. Write the full name of each amino acid under each residue. (Note: pKa of side chain E is ~4.1)

(b) What is the isoelectric point of this peptide? Be sure to show how you reached this number.

(c) You would like to prepare a solution containing this peptide. What pH would you choose for this solution? Explain.

Answer 1

In SMELLY, S is Serine, M is methionine, E is Glutamic acid, L is Leucine and Y is Tyrosine.

Answer a) Structure is

Answer b)

The ionizable groups are N-terminal amino of Serine (pKa = 9.15), C-terminal COOH of Tyrosine (pKa = 2.20) and side chain COOH in glutamic acid (pKa = 4.10)

The range of pH and overall charges for the peptide is as

pH	charge of C-terminal	Charge on N-terminal	Charge on side chain of E	Overall charge
0-2.19	0	+1	0	+1
2.20-4.09	-1	+1	0	0
4.10-9.14	-1	+1	-1	-1
9.15- 14.00	-1	0	-1	-2

As zero charge is between 2.20 to 4.09,

so pI = (2.20+4.09)/2 = 3.15

Answer c)

As the peptide has net zero charge from pH 2.20 to 4.19, the peptide would be least soluble.

The peptide has three ionizable groups, so, it would be best soluble when all three are ionized that would be in pH range 4.10 to 9.14.

Because of the charged groups interaction with water or any other polar solvent would be best and hence more will be the solubility.