Department of Chemistry, ‡Department of Molecular Medicine, §Natural Products Library Initiative at the Scripps Research Institute, and ∥Department of Immunology and Microbiology, The Scripps Research Institute , Jupiter, Florida 33458, United States.
Org Lett. 2017 Nov 17;19(22):6192-6195. doi: 10.1021/acs.orglett.7b03120. Epub 2017 Oct 31.
A new anthraquinone-fused enediyne, yangpumicin A (YPM A, 1), along with four Bergman cyclization congeners (YPM B-E, 2-5), was isolated from Micromonospora yangpuensis DSM 45577 after mining enediyne biosynthetic gene clusters from public actinobacterial genome databases and prioritizing the hits by an enediyne genome neighborhood network analysis for discovery. YPM A is potent against a broad spectrum of human cancer cell lines. The discovery of 1 provides new opportunities for the functionalization of enediynes to develop new conjugation chemistries for antibody-drug conjugates.
从放线菌公共基因组数据库中挖掘烯二炔生物合成基因簇，并通过烯二炔基因组邻域网络分析对命中物进行优先级排序，以发现目标产物，从 Micromonospora yangpuensis DSM 45577 中分离得到一种新型蒽醌融合烯二炔，扬普霉素 A（YPM A，1），以及四个 Bergman 环化同系物（YPM B-E，2-5）。YPM A 对广谱的人类癌细胞系具有很强的活性。1 的发现为烯二炔的功能化提供了新的机会，可开发用于抗体药物偶联物的新偶联化学。
