Chloptosin, an apoptosis-inducing dimeric cyclohexapeptide produced by Streptomyces.
In the course of screening for apoptosis-inducing agents, chloptosin (1) was isolated from the culture broth of Streptomyces. The dumbbell-type structure of the dimeric cyclohexapeptide consisting of D-valine, (3S)- and (3R)-piperazic acids, O-methyl-L-serine, D-threonine, and (2S,3aR,8aR)-6-chloro-3a-hydroxy-2,3,3a, 8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid was elucidated by spectroscopic and chemical degradation studies. The amino acid components in each cyclohexapeptide domain were presented in alternating R and S configurations. Chloptosin (1) was found to induce apoptotic activity in apoptosis-resistant human pancreatic adenocarcinoma cell line AsPC-1 and showed a strong antimicrobial activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus.
Umezawa
K
K
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-0061, Japan. umezawa@applc.keio.ac.jp
Ikeda
Y
Y
Uchihata
Y
Y
Naganawa
H
H
Kondo
S
S
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D006868:Hydrolysis; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification*; D011724:Pyridazines / Q000737:chemistry / Q000302:isolation & purification*; D013057:Spectrum Analysis; D013211:Staphylococcus aureus / Q000187:drug effects; D013302:Streptomyces / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; D011724:Pyridazines