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Antibiotics
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We are currently interested in designing and syntheisizing water soluble receptors that will inhibit bacterial cell wall biosynthesis. Bacterial resistance to clinical antibiotics has risen dramatically over the last decade. For example, the percent of enterococci mosocomial isolates resistant to Vancomycin has increased from 0.3 in 1989 to 14.2 in 1996 and still even higher today. Equally concerning is the possibility that methicillin-resistant Staphylococcus aureus (MRSA) may eventually acquire vancomycin resistance by exchanging genetic information with vancomycin-resistant enterococci. If MRSA acquires vancomycin resistance, this could lead to bacteria with extremely limited susceptibility to any abtibiotics currently available. The alarming increase in multi-drug resistant bacteria as well as the possibility that resistant organisms may acquire greater resistance through genetic exchange among pathogens is a strong indicator that the development of new antibacterial agents should be an important endeavor for chemists. |
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| We use molecular modeling coupled with energy minimization and dynamics experiments to generate peptide based receptors designed to bind bacterial nascent cell wall peptides untimately leading to the development of novel antibiotics. Modeling protocols have been developed to generate receptor:peptide complexes that are inspired by a prevalent structural motif found in proteins, the three-stranded antiparallel b-sheet. Synthetic strategies for the preparation of the receptors on solid support are being developed allowing the generation of focused combinatorial libraries of receptor molecules and the facile screening of their binding efficiencies. |