Oligomers of glycamino acid.
Glycamino acids, a family of sugar amino acids, are derivatives of C-glycosides that possesses a carboxyl group at the C-1 position and an amino group replacing one of the hydroxyl groups at either the C-2, 3, 4, or 6 position. We have prepared a series of glucose-type glycamino acids as monomeric building blocks: these are derivatives of 2-NH(2)-Glc-beta-CO(2)H 1, 3-NH(2)-Glc-beta-CO(2)H 2, 4-NH(2)-Glc-beta-CO(2)H 3, and 6-NH(2)-Glc-beta-CO(2)H 4 and constructed four types of homo-oligomers, beta(1-->2)-linked I, beta(1-->3)-linked II, beta(1-->4)-linked III, and beta(1-->6)-linked IV, employing the well-established N-Boc and BOP strategy. CD and NMR spectral studies of these oligomers suggested that only the beta(1-->2)-linked homo-oligomer possessed a helical structure that seems to be predetermined by the linkage position. Homo-oligomers with beta(1-->2)-linkages I and beta(1-->6)-linkages IV were also subjected to O-sulfation, and these O-sulfated oligomers were found to be able, in a linkage-specific manner, to effectively inhibit L-selectin-mediated cell adhesion, HIV infection, and heparanase activity without the anticoagulant activity associated with naturally occurring sulfated polysaccharides such as heparin.
Suhara
Yoshitomo
Y
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725North Wolfe Street, Baltimore, MD 21205, USA.
Yamaguchi
Yoshiki
Y
Collins
Brian
B
Schnaar
Ronald L
RL
Yanagishita
Masaki
M
Hildreth
James E K
JE
Shimada
Ichio
I
Ichikawa
Yoshitaka
Y
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000494:pharmacology; D002236:Carbohydrate Conformation; D002448:Cell Adhesion / Q000187:drug effects; D002942:Circular Dichroism; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006678:HIV / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D009844:Oligosaccharides / Q000737:chemistry* / Q000494:pharmacology*; D019087:Selectins / Q000378:metabolism; D000099175:Heparanase
D000596:Amino Acids; D019380:Anti-HIV Agents; D005966:Glucuronidase; D006027:Glycosides; D009844:Oligosaccharides; D019087:Selectins; D000099175:Heparanase