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 language | English (US) |
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Pages (from-to) | 5984-5988 |
Number of pages | 5 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 19 |
Issue number | 20 |
DOIs | |
State | Published - Oct 15 2011 |
Funding
This study was supported by the Japan Society for the Promotion of Science (Grant-in-Aid for Young Scientists 20890002 to M.W. and Grant 21390028 to S.S.) and the Uehara Memorial Foundation (to M.W.). The authors are grateful to Sanyo Fine Co., Ltd for the gift of the chiral epichlorohydrins.
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