Four classes of structurally unusual peptides from two marine-derived fungi: structures and bioactivities

TETRAHEDRON

卷:63

Article

Boot, Claudia M.^1,2  Amagata, Taro¹  Tenney, Karen¹  Compton, Jennifer E.¹  Pietraszkiewicz, Halina³  Valeriote, Frederick A.³  Crews, Phillip^1,2 

[1] Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA

[2] Univ Calif Santa Cruz, Dept Ocean Sci, Santa Cruz, CA 95064 USA

[3] Henry Ford Hlth Syst, Dept Internal Med, Div Hematol & Oncol, Detroit, MI 48202 USA

关键词: marine-derived fungi;    efrapeptin;    destruxin;    RHM;   

DOI  :  10.1016/j.tet.2007.06.034

来源: Elsevier

【 摘 要 】

The structures and biological properties of peptides produced by two genera of marine-derived fungi, an atypical Acremonium sp., and a Metarrhizium sp., were explored. The Acremonium strain was isolated from a marine sponge and has previously been shown by our group to produce peptides from the efrapeptin and RHM families. The isolation and structural elucidation of the new linear pentadecapeptides efrapeptins E alpha (1) and H (2) and N-methylated octapeptides RHM3 (3) and RHM4 (4) were carried out through a combination of 1D and 2D NMR techniques and tandem MS. Additional known efrapeptins E, F, and G and the known syctalidamides A and B were also isolated. The absolute configurations of 1-4 are proposed to be the same as the original compound families. The marine sponge-derived Metarrhizium sp. was shown to produce destruxin cyclic depsipeptides including A, B, B2, desmethyl B, E chlorohydrin, and E2 chlorohydrin. Efrapeptins Ea (1), F, and G each displayed IC(50)s of 1.3 nM against H125 cells, and destruxin E2 chlorohydrin displayed an IC50 of 160 nM against HCT-116 cells. An initial therapeutic assessment suggested a continuous (168 h) exposure of at least 2 ng/mL, or a daily (24 h) exposure of at least 300 ng/mL for H125 cells treated with efrapeptin G, and a continuous (168 h) exposure of at least 190 ng/mL for HCT-116 cells treated with destruxin E2 chlorohydrin, will cause 90% tumor cell death in vitro. (C) 2007 Elsevier Ltd. All rights reserved.

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