A polyvalent binding strategy will be used to develop antibiotics that are active against vancomycin resistant bacteria. A combination of vancomycin binding and membrane insertion moieties will be used to increase the overall affinity of the polymer for bacterial cell walls. The membrane binding portion will be further developed into a general strategy for binding and antibiotic action by the synthesis of polyvalent forms of host defense peptides that show wide antibacterial activity. These molecules should retain their specificity for bacterial membranes while increasing their potency via the cooperative nature of the polyvalent binding. Systems will be analyzed using surface plasmon resonance and cell culture techniques.
Krishnamurthy, Vijay M; Quinton, Lee J; Estroff, Lara A et al. (2006) Promotion of opsonization by antibodies and phagocytosis of Gram-positive bacteria by a bifunctional polyacrylamide. Biomaterials 27:3663-74 |