Thiazomycins, thiazolyl peptide antibiotics from Amycolatopsis fastidiosa.

Abstract

Thiazolyl peptides are a class of highly rigid trimacrocyclic compounds consisting of varying but large numbers of thiazole rings. The need for new antibacterial agents to treat infections caused by resistant bacteria prompted a reinvestigation of this class, leading to the previous isolation of thiazolyl peptides, namely, thiazomycin (5) and thiazomycin A (6), congeners of nocathiacins (1-4). Continued chemical screening led to the isolation of six new thiazolyl peptide congeners (8-13), of which three had truncated structures lacking an indole residue. From these, compound 8 showed activity similar to thiazomycin. Two compounds (9 and 10) showed intermediate activities, and the three truncated compounds (11-13) were essentially inactive. The discovery of the truncated compounds revealed the minimal structural requirements for activity and suggested probable biosynthetic pathways for more advanced compounds. The isolation, structure elucidation, antibacterial activity, and proposed biogenesis of thiazomycins are herein described.

• Authors: Chaowei Zhang, Kithsiri Herath, Hiranthi Jayasuriya, John G Ondeyka, Deborah L Zink, James Occi, Gwyneth Birdsall, Jayashree Venugopal, Misti Ushio, Bruce Burgess, Prakash Masurekar, John F Barrett, Sheo B Singh
• Journal: Journal of natural products (J Nat Prod) Vol. 72 Issue 5 Pg. 841-7 (May 22 2009) ISSN: 1520-6025 [Electronic] United States
• PMID: 19334707 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Peptides
• Peptides, Cyclic
• Thiazoles
• thiazomycin

Topics

• Actinomycetales (chemistry)
• Anti-Bacterial Agents (chemistry, isolation & purification, pharmacology)
• Combinatorial Chemistry Techniques
• Microbial Sensitivity Tests
• Molecular Structure
• Peptides (chemistry, isolation & purification, pharmacology)
• Peptides, Cyclic (chemistry, isolation & purification, pharmacology)
• Stereoisomerism
• Thiazoles (chemistry, isolation & purification, pharmacology)