ハタ　ユカコ
  畑　友佳子
   所属   薬学部 薬学科
   職種   講師
言語種別 英語
発行・発表の年月 2015
形態種別 学術論文
査読 査読あり
標題 3‑Fluoroazetidinecarboxylic Acids and trans,trans-3,4-Difluoroprolineas Peptide Scaffolds: Inhibition of Pancreatic Cancer Cell Growth by a Fluoroazetidine Iminosugar
執筆形態 共著
掲載誌名 J.O.C.
掲載区分国外
巻・号・頁 80,pp.4244-4258
著者・共著者 Zilei Liu, Sarah F. Jenkinson, Tom Vermaas, Isao Adachi, Mark R. Wormald, Yukako Hata,
Yukiko Kurashima, Akira Kaji, Chu-Yi Yu, Atsushi Kato and George W. J. Fleet
概要 Reverse aldol opening renders amides of
3-hydroxyazetidinecarboxylic acids (3-OH-Aze) unstable above
pH 8. Aze, found in sugar beet, is mis-incorporated for proline
in peptides in humans and is associated with multiple sclerosis
and teratogenesis. Aze-containing peptides may be oxygenated
by prolyl hydroxylases resulting in potential damage of the
protein by a reverse aldol of the hydroxyazetidine; this, rather
than changes in conformation, may account for the deleterious
effects of Aze. This paper describes the synthesis of 3-fluoro-Aze
amino acids as hydroxy-Aze analogues which are not susceptible
to aldol cleavage. 4-(Azidomethyl)-3-fluoro-Aze and 3,4-difluoroproline are new peptide building blocks. trans,trans-2,4-Dihydroxy-
3-fluoroazetidine, an iminosugar, inhibits the growth of pancreatic cancer cells to a similar degree as gemcitabine.