Title
Manipulating Active Structure and Function of Cationic Antimicrobial Peptide CM15 by the Polysulfonated Drug Suramin: A Step Closer to in vivo Complexity
Author
Mayra Quemé-Peña, Tünde Juhász, Judith Mihály, Imola Csilla Szigyártó, Kata Horváti, Szilvia Bősze, Judit Henczkó, Bernadett Pályi, Csaba Németh, Zoltán Varga Ferenc Zsila, Tamás Beke-Somfai
Year
2019
Journal
ChemBioChem
Abstract
Antimicrobial peptides (AMPs) kill bacteria by targeting their membranes via various mechanisms involving peptide assembly often coupled with disorder‐to‐order structural transition. However, similar conformational changes were recently reported for several AMPs, where small organic molecules of both endogenous and exogenous origin induced folded peptide conformation. Thus, function of AMPs and natural host defense peptides can be significantly affected by the local complex molecular environment in vivo, nonetheless this area is hardly explored. To address the relevance of such interactions on structure and function, herein we tested the effect of the therapeutic drug suramin on the membrane activity and antibacterial efficiency of a potent hybrid AMP, CM15. Results provided insight to a dynamic system where peptide interaction with lipid bilayers is interfered with the competitive binding of CM15 to suramin, resulting in an equilibrium dependent on peptide‐to‐drug ratio and vesicle surface charge. In vitro bacterial tests show that when CM15‐suramin complex formation dominates over membrane binding, antimicrobial activity is abolished. Based on this case study, it is proposed that small molecule secondary structure regulators can modify AMP function, which should be considered and could potentially be exploited in future development of AMP‐based antimicrobial agents.
Instrument
J-1500
Keywords
Circular dichroism, Secondary structure, Membrane interactions, Ligand binding, Protein folding, Biochemistry, Pharmaceutical