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Combinatorial modification of natural products: synthesis and in vitro analysis of derivatives of thiazole peptide antibiotic GE2270 A: A-ring modifications

✍ Scribed by Jeffrey Clough; Shaoqing Chen; Eric M. Gordon; Corinne Hackbarth; Stuart Lam; Joaquim Trias; Richard J. White; Gianpaolo Candiani; Stefano Donadio; Gabriella Romanò; Romeo Ciabatti; Jeffrey W. Jacobs


Book ID
104364105
Publisher
Elsevier Science
Year
2003
Tongue
English
Weight
228 KB
Volume
13
Category
Article
ISSN
0960-894X

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✦ Synopsis


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 mg/mL) and vancomycin resistant Enterococcus spp. (VRE; MIC 90 =0.03 mg/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.