Kinetic Interactions between Cyclolinopeptides and Immobilized Human Serum Albumin by Surface Plasmon Resonance.

Abstract

Cyclolinopeptides (CLs) are octa-, nona-, and decapeptides present in flaxseed (Linum usitatissimum L.) that may have immunosuppressive and antitumor activities, but little is known of their pharmacokinetics. Human serum albumin (HSA), the most abundant blood protein, is an important mediator of organic solute flux, and hence when compounds bind this protein, it potentially affects both their availability and efficacy. Quantitative thermodynamic analysis of the interaction of compounds with HSA is important in the development of biomedical applications. A surface plasmon resonance (SPR) biosensor was utilized to reliably determine binding constants for several CLs with HSA. The maximum binding response of [1-9-NαC]-CLA/HSA was almost 20-fold higher than that of [1-8-NαC],[1-MetO]-CLE/HSA. Through analysis of an array of peptides, it was possible to correlate the impact of structural changes on CL binding. The oxidation of sulfur in methionine (Met) residues formed methionine S-oxide (MetO) and reduced binding significantly. Most strikingly, the further oxidation of MetO to S,S-dioxide (MetO2) produced CLs with stronger binding. The large impact on binding by relatively small modifications of methionine containing CLs suggested that small changes in methionine oxidation can disrupt hydrophobic interaction, the predominant intermolecular force stabilizing the complex between CLs and HSA. SPR binding studies may aid in understanding the fate of CLs after consumption of flaxseed or flaxseed products or the development of CLs as drugs or drug carriers.