Molecular analysis and therapeutic applications of human serum albumin-fatty acid interactions

Human serum albumin (hSA) is the major carrier protein for fatty acids (FAs) in plasma. Its ability to bind multiple FA moieties with moderate to high affinity has inspired the use of FA conjugation as a safe and natural platform to generate long-lasting therapeutics with enhanced pharmacokinetic properties and superior efficacy. In this frame, the choice of the FA is crucial and a comprehensive elucidation of the molecular interactions of FAs with hSA cannot be left out of consideration. To this intent, we report here a comparative analysis of the binding mode of different FA moieties with hSA. The choice among different albumin-binding FAs and how this influence the pharmacokinetics properties of a broad spectrum of therapeutic molecules will be discussed including a critical description of some clinically relevant FA conjugated therapeutics.

Automated summary

Human serum albumin is a major carrier protein for fatty acids in plasma, and its ability to bind multiple fatty acid moieties with moderate to high affinity inspired the use of fatty acid conjugation as a safe and natural platform to generate long-lasting therapeutics with enhanced pharmacokinetic properties and superior efficacy. The choice of fatty acids is crucial for the pharmacokinetics properties of therapeutic molecules.