(530f) Molecular Insight on the Molecular Mechanisms for the Biological Activity of Dendritic Amphiphiles on Biological Membranes

Lipid bilayers are central in the study and understanding of biological membranes. Their structure, function, and activity are directly related to the composition and molecular properties of the membrane constituents. In an effort to understand the antimicrobial activity of a new class of dendritic amphiphiles (3CAmn)?potentially safe, effective, acceptable, and affordable topical microbicides with anti-HIV, anti-STD pathogens, antibacterial, and antifungal activities [1], we combine experimental and computational techniques to obtain insight into how these amphiphiles interact with lipid bilayers. Because 3CAmn are lipid-like compounds, their interactions with the lipid bilayer of biological membranes result in biophysical changes in the structure and dynamics of the membranes. Wide-angle (WAXD) and small-angle (SAXD) X-ray diffraction on model DPPC membranes show systematic changes to the membrane structure and, consequently, the phase transition due to interaction with these dendritic amphiphiles. Molecular dynamics simulations of these structures reveal the specific molecular mechanisms associated with the changes to the membrane structure. This study represents a multi-scale modeling approach to design, develop, and understand the biological activities of this homologous series of dendritic amphiphiles that include very long chains.

[1] J. Antimicrob. Chemother. 51, 451?458 (2007).