Patent ID: 8268581

Claim:
A method for increasing the stability of a polypeptide, wherein the last two amino acid residues of the carboxy terminal sequence of the polypeptide are independently selected from Ala, Cys, Ile, Leu, Ser, Thr, and Val, and wherein the antepenultimate amino acid residue of the carboxy terminal sequence of the polypeptide is not Asp, Gly, Glu or His, against degradation by a C-terminal specific mycobacterium protease, comprising the step of altering one or more of the last three amino acid residues at the carboxy terminus of the polypeptide, wherein the alteration is selected from the group consisting of amino acid substitution, amino acid insertion, and amino acid deletion, and wherein the alteration results in at least one of: (a) one or both of the last two amino acid residues of the carboxy terminal sequence of the polypeptide being selected from the group consisting of Arg, Asp, Glu, Gly, His, Lys, Phe, Pro, Trp, and Tyr, and (b) the antepenultimate residue of the carboxy terminal sequence of the polypeptide being selected from the group consisting of Asp, Gly, Glu, and His; and measuring the stability of the altered polypeptide against degradation by the C-terminal specific mycobacterium protease, whereby the stability of the altered polypeptide against degradation by the C-terminal specific mycobacterium protease is increased as compared to the unaltered polypeptide.