Nucleoside peptides. 10. Synthesis and T-cell immunostimulatory properties of certain peptide derivatives of 6-azacadeguomycin.
Several amino acid and peptide conjugates of 6-azacadeguomycin (6-amino-1-beta-D-ribofuranosyl-4,5-dihydro-4-oxopyrazolo[3,4-d]py rimidine- 3-carboxylic acid, 2) have been prepared in good yields, via a two-step procedure involving 1-hydroxybenzotriazole and 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide hydrochloride mediated coupling of 2 with an appropriately protected amino acid or peptide, followed by ammonolysis. Thus, condensation of 2 with L-phenylalanine methyl ester, glycine ethyl ester, and L-glutamic acid diethyl ester gave the corresponding protected linear nucleoside peptides (3, 5 and 7, respectively). Subsequent ammonolysis of 3, 5 and 7 furnished L-phenylalanine amide (4), glycine amide (6) and L-glutamic acid diamide (8) conjugates of 6-azacadeguomycin, respectively. Saponification of 7 gave the corresponding L-glutamic acid derivative 9. A similar coupling of 2 with L-phenylalaninyl-N epsilon-nitro-L-arginine methyl ester trifluoroacetate and subsequent ammonolysis (after catalytic hydrogenation) gave L-phenylalaninyl-L-arginine amide conjugate (12) of 6-azacadeguomycin. Compounds 2, 4, 6, 8, 9, and 12 were evaluated for their ability to potentiate T-cell responses to plant mitogens, in comparison with cadeguomycin (1). Compounds 4, 6, and 9 exhibited an increase in the T-cell proliferation in a dose-dependent manner.
ICN Nucleic Acid Research Institute, Costa Mesa, California 92626.
K
K
Ramasamy
B S
BS
Sharma
W B
WB
Jolley
R K
RK
Robins
G R
GR
Revankar
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D006151:Guanosine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation / Q000187:drug effects
D000900:Anti-Bacterial Agents; D006151:Guanosine; C045967:6-azacadeguomycin