Determination of the binding sites of toluene diisocyanate on human serum albumin by tandem mass spectrometry

摘要

TDI binding results in diverse chemistry, including intra- and inter-molecular cross linking, TDI hydrolysis and self-polymerization. The number of albumin residues to which TDI binds increases with increasing isocyanate concentration, from ten residues at 5:1 mole ratio to 37 residues at 40:1 mole ratio (34 K, 2 Q, and N-terminal D). TDI binding at Lys results in missed trypsin cleavage. TDI binds a subset of 59 total lysines, all of which are solvent accessible. TDI binds through the uncharged -NH_(2) rather than -NH_(3)~(+); TDI binding sites correlate favorably with known residue pK_(a).