Site-specific chemoenzymatic protein modifications

A method for modifying a protein, comprising:

• providing a target protein having at least one lysine residue;
• contacting the target protein with a modifying compound having the formula
• R1-(Leu)x-Gln-(Gly)y-(A-W—B—R2)z in the presence of a microbial transglutaminase to form a modified protein;
• wherein x is 0 or 1;
• y is 0 or 1;
• z is 0 or 1;
• R1 is selected from the group consisting of:
• acetyl,
• wherein R4 is selected from —H, —N3, and
• W is selected from:
• C1-C6 linear or branched alkyl or polyethylene glycol having a molecular weight of between about 40 and about 80,000 amu;
• A is absent or selected from —O—, —NH—, and —S—;
• B is absent or selected from —O—, —C(O)—, —NH—, —C(O)NH—, —NHC(O)—, —NHC(O)O—, —OC(O)NH—, —OC(O)O—, —C═N(OH)—, —S(O2)—, —NHS(O2)—, —S(O2)NH—, —S(O)—, —NHS(O)—, —S(O)NH—;
• —C(O)O—, —OC(O)—, —S—, ═NH—O—, ═NH—NH— and ═NH—N(C1-C20alkyl)-;
• R2 is selected from the group consisting of:
• a fatty acid, linear or branched C1-C3 alkyl-N3, cyclooctynyl, fluorophore, polysaccharide, —CH(OCH3)2,
• each n is an integer independently selected from 0 to 6;
• each Q is selected from H and NO2.