MEDI 278 |
| Natural antimicrobial peptides (AMPs) secreted by most organisms have been investigated as a potential source of new antibiotics. Our recent studies indicate that a multivalent strategy of polymerized AMPs can enhance the potency of monomeric peptides. However, the mechanism by which multivalent AMPs kill bacterial pathogens has yet to be explored. It is generally accepted that AMPs lead to permeation of the bacterial cell membrane. Two phases of interaction between AMPs and membranes have been detected: (1) binding by electrostatic interactions, and (2) assembly of bound AMPs to the membrane. Our results support this biphasic model, we find adding charges can enhance binding without facilitating assembly. Initial attachment of arginine peptides are electrostatically driven, while presence of typtophan favors an intercalation process at the interface between the headgroups and core of the membrane. Promoting assembly requires a different interaction, and we will describe models that alter the balance between them. |
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Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Medicinal Chemistry |