Synthesis of a series of 3,4-methanoarginines as side-chain conformationally restricted analogues of arginine

Mizuki Watanabe, Kazuya Yamaguchi, Wei Tang, Keisuke Yoshida, Richard B Silverman, Mitsuhiro Arisawa, Satoshi Shuto*

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

A series of optically active stereoisomers of 3,4-methanoarginine (1-4 and ent-1-ent-4) with trans/cis, d/l, and syn/anti stereochemical diversity, the side-chains of which were restricted in various special arrangements, was designed as biologically useful arginine mimetics. These conformationally restricted arginine analogues were synthesized effectively by using a series of chiral 3,4-methanoamino acid equivalents (7-10 and ent-7-ent-10) as the key synthetic units. Their biological evaluation with three isoforms of nitric oxide synthase showed that trans-3,4-methano-l-syn-arginine (2) was a good substrate, having close potency to l-arginine, and isoforms selectivities were also similar to those of l-arginine.

Original languageEnglish (US)
Pages (from-to)5984-5988
Number of pages5
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number20
DOIs
StatePublished - Oct 15 2011

Keywords

  • Arginine analogue
  • Conformational restriction
  • Cyclopropane
  • Nitric oxide synthase
  • Stereochemical diversity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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