title: Combinatorial modification of natural products: synthesis and in vitro analysis of derivatives of thiazole peptide antibiotic GE2270 A: A-ring modifications.
abstract: Thiazole peptide GE2270 A (1) possesses potent antimicrobial activity against many gram-positive pathogens, including methicillin resistant Staphylococcus aureus (S. aureus, MRSA; MIC(90)=0.06 microg/mL) and vancomycin resistant Enterococcus spp. (VRE; MIC(90)=0.03 microg/mL); however its poor aqueous solubility has prohibited its development for the clinical treatment of infections. An integrated combinatorial and medicinal chemistry program was employed to identify derivatives of 1 that retain activity but possess greatly enhanced aqueous solubility.
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D008826:Microbial Sensitivity Tests; D010455:Peptides; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D001688:Biological Products; D010455:Peptides; D010456:Peptides, Cyclic; D013844:Thiazoles; C068122:GE 2270 A