Question

Peptides hold great potential for the cancer therapy because of their ease of rational design. During your first undergraduate research project, you conducted a screen to find peptides that inhibit proliferation of cancer cells. From a large library of 9-residue-long peptides, you got a hit!

Unfortunately, someone mislabeled the vial containing the active peptide, so now you can’t be sure of its entire sequence.

The 3rd amino acid could be any one of the 20 amino acids!!

           M I   _ S E L F I E

Luckily, you collected information about the net charge of all the peptides in your library as a function of pH

(a) Based on the information below, what is the full sequence of this peptide? (please provide a rationale for your answer)

At pH 3, net charge = +1
At pH 7, net charge = -1
At pH 12, net charge = -2

Peptide Sequence:

(b) Estimate the isoelectic point (pI) of the peptide and show how you determined this value.

Answer 1

The Pi of the peptide should be above 8 and below 12.48. Because if we consider at pH 3 the net charge is +1 if we add zero charge for the N terminal NH2 group and considering missing amino acid as an arginine then the charge at pH would be zero. However, we can not go beyond 12.48, because it is the pka of arginine and it may lose the charge if we move above 12.48. Therefore, from the given information it can be concluded that PI would be in between 8 to 12.