Ligand Design with Accelerated Disulfide Formation with Serum Albumin to Extend Blood Retention.

We proposed a novel ligand for the interaction with human serum albumin (HSA) to extend the blood half-life of small molecular weight therapeutics. The ligand features an alkyl chain and an activated disulfide to allow binding to the hydrophobic pockets of HSA and the formation of disulfide to Cys34 of HSA, thereby minimizing the initial renal clearance. The dual nature of the ligand-HSA bonding was expected to give the ligand long blood retention.