Peter A. Smith;Floyd E. Romesberg;Tucker C. Roberts
发明人:
Floyd E. Romesberg,Peter A. Smith,Tucker C. Roberts
申请号：
US15008881
公开号：
US20160297851A1
申请日:
2016.01.28
申请国别(地区):
US
年份:
2016
代理人:
摘要：
Arylomycin analogs are provided, wherein the analogs can have broad spectrum bioactivity. Resistance to the antibiotic bioactivity of natural product arylomycin in a range of pathogenic bacterial species has been found to depend upon single amino acid mutations at defined positions of bacterial Signal Peptidases (SPases), wherein the presence of a proline residue confers arylomycin resistance. Arylomycin analogs are provided herein that can overcome that resistance and provide for a broader spectrum of antibiotic bioactivity than can natural product arylomycins such as arylomycin A2. Methods for determining if a bacterial strain is susceptible to narrow spectrum arylomycin antibiotics, or if a broad spectrum analog is required for treatment, is provided. Pharmaceutical compositions and methods of treatment of bacterial infections, and methods of synthesis of arylomycin analogs, are provided.
