YM-216391, a Novel Cytotoxic Cyclic Peptide from Streptomyces nobilis

Sohda, Kin-ya; Hiramoto, Masashi; Suzumura, Ken-ichi; Takebayashi, Yukihiro; Suzuki, Kenichi; Tanaka, Akihiro

doi:10.1038/ja.2005.3

Cited by 30 publications

(41 citation statements)

References 7 publications

(5 reference statements)

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“…613 NMR structure determination revealed YM-216391 to be a cyclic, pentazole-containing peptide, similar to the telomerase inhibitor telomestatin (Figure 29). 614 All but one amino acid (Val) of the core peptide have been modified; Marfey’s analysis confirmed the presence of D- allo -Ile. The complete stereochemistry has also been confirmed through total synthesis.…”

Section: Miscellaneous Azol(in)e-containing Rippsmentioning

confidence: 95%

YcaO-Dependent Posttranslational Amide Activation: Biosynthesis, Structure, and Function

et al. 2017

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With advances in sequencing technology, uncharacterized proteins and domains of unknown function (DUFs) are rapidly accumulating in sequence databases and offer an opportunity to discover new protein chemistry and reaction mechanisms. The focus of this review, the formerly enigmatic YcaO superfamily (DUF181), has been found to catalyze a unique phosphorylation of a ribosomal peptide backbone amide upon attack by different nucleophiles. Established nucleophiles are the side chains of Cys, Ser, and Thr which gives rise to azoline/azole biosynthesis in ribosomally synthesized and posttranslationally modified peptide (RiPP) natural products. However, much remains unknown about the potential for YcaO proteins to collaborate with other nucleophiles. Recent work suggests potential in forming thioamides, macroamidines, and possibly additional post-translational modifications. This review covers all knowledge through mid-2016 regarding the biosynthetic gene clusters (BGCs), natural products, functions, mechanisms, and applications of YcaO proteins and outlines likely future research directions for this protein superfamily.

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Section: Miscellaneous Azol(in)e-containing Rippsmentioning

confidence: 95%

YcaO-Dependent Posttranslational Amide Activation: Biosynthesis, Structure, and Function

et al. 2017

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“…Following conversion of the thioamide unit in 79 into the thiazoline 80, oxidation with MnO 2 in CH 2 Cl 2 finally gave the cyclopeptide 81 [a] 20 D −56 (c = 0.5, CHCl 3 ) whose 1 H NMR and 13 C NMR spectroscopic data matched very closely those reported for naturally derived YM-216391. Following the completion of our synthesis, which allowed us to establish the relative stereochemistry shown in structure 81 for YM-216391, Sohda et al 34 published details of their investigations of the structure of YM216391 from Streptomyces nobilis. The studies of Sohda et al led to the same assignment of relative stereochemistry for YM216391 as we had determined by synthesis, but the natural product showed [a] 25 D +48 (c = 0.1, CH 3 CN), i.e.…”

Section: Total Synthesis Of (−)-Ym-216391 (2)mentioning

confidence: 97%

Novel polyoxazole-based cyclopeptides from Streptomyces sp. Total synthesis of the cyclopeptide YM-216391 and synthetic studies towards telomestatin

2008

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A convergent, complementary, synthetic approach to the contiguously linked tris-oxazole units 10, 11 and 12 in telomestatin (1) and YM-216391 (2) is described. The route involves coupling reactions between oxazole 4-carboxylic acids, viz 16a, 16c, 16d and oxazole 2-substituted methylamines, viz 16b, 16e, 17, leading to the amides 18 and 21, followed by cyclodehydrations to the corresponding bis-oxazole oxazolines, e.g. 19, and oxidations of the latter using well-established protocols. The tris-oxazoles 11 and 12 were next converted stepwise into the hexa-oxazole bis-macrolactams 33. Although the bis-macrolactams 33 (cf. 28) could be converted into the corresponding oxazoline-hexa-oxazoles 34 and to the enamides 35, neither of these intermediates could be elaborated to the hepta-oxazole 30en route to telomestatin 1. Likewise, neither the hexa-oxazole 47 or application of an intramolecular Hantzsch oxazole ring-forming reaction from 44b allowed access to the advanced polyoxazole-macrolactam intermediates 48 and 30a, respectively, towards telomestatin. Combination of the tris-oxazole based methylamine 70 with the dipeptide carboxylic acid 71 derived from D-valine and L-isoleucine, leads to the corresponding amide which, in two straightforward steps, is converted into the -amino acid 78. Macrolactamisation of 78, using HATU, next produces the cyclopeptide 79 which is then elaborated to the thiazole and oxazole based cyclopeptide YM-216391 (2). The synthetic cyclopeptide 2 is shown to be the enantiomer of the natural product isolated from Streptomyces nobilis.

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“…No antiviral activity has been reported for 38 [10]; however, its analogue, which contains the 4,2bisheterocyclic tandem pairs, shows antiviral activity and therefore emerges as a useful scaffold for the synthesis of new antiviral agents [57]. The structure of 39 comprises a sequence of five azoles (trisoxazole, a thiazole, and phenyloxazole), originated from Ser, Cys, and Phe, respectively, linked via a Gly-Val-Ile tripeptide tether [58]. Compound 39 shares both the structure and biological homology with Telomestatin [58] a potent telomerase inhibitor isolated from Streptomyces anulatus with promising potential use in cancer chemotherapy.…”

Section: Leucamide Amentioning

confidence: 99%

“…The structure of 39 comprises a sequence of five azoles (trisoxazole, a thiazole, and phenyloxazole), originated from Ser, Cys, and Phe, respectively, linked via a Gly-Val-Ile tripeptide tether [58]. Compound 39 shares both the structure and biological homology with Telomestatin [58] a potent telomerase inhibitor isolated from Streptomyces anulatus with promising potential use in cancer chemotherapy. Biological experiments suggest that 39 is cytotoxic towards human cervical cancer HeLa S3 cells and other human cancer cell lines.…”

Section: Leucamide Amentioning

confidence: 99%