ABSTRACT
Several immunosuppressants, ISP-I [(2S,3R,4R)-(E)-2-amino-3,4-dihydroxy-2-(hydroxymethyl)-14-oxoeicos++ +-6-enoic acid, myriocin = thermozymocidin] and mycestericins A-G, were isolated from culture broths of Isaria sinclairii and Mycelia sterilia, respectively. In order to investigate structure-activity relationships, extensive modifications of ISP-I were conducted, and it was established that the fundamental structure possessing the immunosuppressive activity is a symmetrical 2-alkyl-2-aminopropane-1,3-diol. The tetradecyl, pentadecyl, and hexadecyl derivatives prolonged rat skin allograft survival in the combination of LEW donor and F344 recipient and were more effective than cyclosporin A. Among them, 2-amino-2-tetradecylpropane-1,3-diol hydrochloride, ISP-I-55, showed the lowest toxicity. ISP-I-55 is a promising lead compound for the development of effective immunosuppressants for organ transplantations and for the treatment of autoimmune diseases.
Subject(s)
Fatty Acids, Monounsaturated/chemistry , Immunosuppressive Agents/chemical synthesis , Propylene Glycols/chemistry , Acyltransferases/metabolism , Alkylation , Animals , Ascomycota , Eicosanoic Acids/chemistry , Fatty Acids, Unsaturated/chemistry , Interleukin-2/biosynthesis , Mice , Rats , Serine C-Palmitoyltransferase , Skin/drug effects , Spleen/drug effectsABSTRACT
Two polysaccharide fractions, PS1 and PS2 from Lomentaria catenata consisted of D-Gal, L-Gal, D-Glc, D-Xyl, D-GlcA and sulphate. Partial hydrolysis led to the isolation and identification of oligosaccharides indicating the co-existence of an agarose and carrageenan backbone structure, in which D-Glc and D-GlcA residues occur as single units branching at O-3 of -->4)alpha-D-Gal(1--> and O-4 of -->3)beta-D-Gal(1-->, respectively.
Subject(s)
Carrageenan/chemistry , Rhodophyta/chemistry , Sepharose/chemistry , Carbohydrate Sequence , Carrageenan/isolation & purification , Chromatography, Thin Layer , Molecular Sequence Data , Sepharose/isolation & purificationABSTRACT
Methyl alpha- and beta-D-galactopyranosides and 4-O-beta-D-galactopyranosyl-3,6-anhydro-L-galactose dimethylacetal were sulfated with sulfuric acid and dicyclohexylcarbodiimide as a condensation reagent. The sulfated sugars were isolated by ion-exchange chromatography, characterized, and assigned by methylation analyses. On the basis of the yield of each sulfated product that was isolated, sulfation on O-6 appeared to be predominant.