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

Bioorg Med Chem Lett. 2003 Oct 20;13(20):3409-14. doi: 10.1016/s0960-894x(03)00811-4.

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

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Biological Products / chemical synthesis*
  • Biological Products / chemistry
  • Combinatorial Chemistry Techniques
  • Microbial Sensitivity Tests
  • Peptides*
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / chemistry*
  • Thiazoles / chemical synthesis*
  • Thiazoles / chemistry*

Substances

  • Anti-Bacterial Agents
  • Biological Products
  • Peptides
  • Peptides, Cyclic
  • Thiazoles
  • GE 2270 A