RRC ID 38904
著者 Yoshida M, Onda Y, Masuda Y, Doi T.
タイトル Potent oxazoline analog of apratoxin C: Synthesis, biological evaluation, and conformational analysis.
ジャーナル Biopolymers
Abstract In this research, the synthesis, biological evaluation, and conformational analysis of an apratoxin C oxazoline analog (3) have been demonstrated. The preparation of synthetic key intermediate 9 was achieved using an improved strategy that involves commercially available 3-methylglutaric anhydride (12), an enzymatic enantioselective alcoholysis, and a diastereoselective reduction. The Pro-Dtrina (3,7-dihydroxy-2,5,8-trimethylnonanoic acid) moiety 8 was successfully synthesized in a similar manner as our previously reported synthesis of apratoxin C (1). The cyclization precursor 5 was formed after the coupling of Pro-Dtrina 8 with a known tetrapeptide 7 to afford a linear peptide 6, the formation of an oxazoline, and the removal of the protecting groups. Finally, the macrolactamization of 5 with O-(7-aza-1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU)/N,N-diisopropylethylamine (DIEA) furnished an apratoxin C oxazoline analog (3), which exhibited a potent cytotoxicity against HeLa cells (IC50 value of 22 nM) that was comparable with the cytotoxicity of apratoxin C (1) (IC50 value of 4.2 nM). Conformational analyses of 1 and 3 through NMR experiments showed that oxazoline analog 3 formed a tertiary structure that was similar to the apratoxin C (1) structure in CD3 CN, which provided a probable explanation for their comparable cytotoxicities. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 404-414, 2016.
巻・号 106(4)
ページ 404-14
公開日 2016-11-4
DOI 10.1002/bip.22781
PMID 26584466
MeSH Cell Survival / drug effects Cytotoxins / chemical synthesis* Cytotoxins / chemistry* Cytotoxins / pharmacology* Depsipeptides / chemical synthesis* Depsipeptides / chemistry* Depsipeptides / pharmacology* HeLa Cells Humans
IF 1.854
引用数 8
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 HeLa(RCB0007)