Conjugation of testo and testo-Pt(II) with serum proteins: Loading efficacy and protein conformation.

The potential application of hybrid anticancer molecules requires further investigation. There is a great interest in developing new site-specific anticancer agents able to efficiently destroy cancer cells with minimal toxic side effects. Serum proteins are known to play an important role as drug delivery system with important clinical applications. Hence, the conjugation of testo and testo-Pt(II) (two semi-synthetic testosterone derivatives) with human serum albumin HSA), bovine serum albumin (BSA) and beta-lactoglobulin ( β -LG) was investigated in aqueous solution at physiological pH. Multiple spectroscopic methods, thermodynamic analysis and modeling were used to determine the binding efficacy of these bioactive compounds to serum proteins. Drug-protein conjugation occurred via ionic contacts. BSA forms more stable conjugates than HSA and β -LG with the order of stability testo > testo-Pt(II). Major alterations of protein secondary structures were observed upon drug complexation. Serum proteins can be used to deliver these bioactive materials in vitro. [ABSTRACT FROM AUTHOR]