Development of novel peptide antibiotics for vancomycin resistant infection using the “one-bead, one-compound” combinatorial library method

Vancomycin, a glycopeptide antibiotic against Gram-positive bacteria, works by binding tightly to peptidoglycan strands in the bacterial cell wall that terminates in D-Ala-D-Ala and blocks the transglycosylation of nascent peptidoglycan strands [1]. Vancomycin resistant cells have replaced the normal D-Ala-D-Ala peptidoglycan termini with D-AlaDLactate termini that are no longer recognized by vancomycin [2,3]. We hypothesize that by using D-Ala-D-lactate as a probe for screening “one-bead, one-compound” combinatorial chemical libraries [4,5], antibacterial agents that inhibit vancomycin resistant bacteria can be isolated.