Novel side-chain glucosylated and adamantylated [Asp(2)/Glu(2)]enkephalin analogs: synthesis and in vitro growth inhibition of human tumor cells.
A series of new backbone-modified Leu- and Met-enkephalin analogs (13-20 a and b) were synthesized. Backbone manipulations involved the replacement of the Gly(2) residue in Tyr-Gly-Gly-Phe-Leu/Met with side-chain glucosylated or adamantylated D/L-aspartic or -glutamic acids. The in vitro antiproliferative activity of these compounds was evaluated for several cell lines and the results were compared with the effect of Met-enkephalin, the native opioid growth factor. The tested compounds modestly inhibited the growth of the tumor cells (20-50% inhibition at millimolar concentrations). Among the tested compounds, Tyr-D-Glu(AdNH)-Gly-Phe-Met (20b) showed significant antiproliferative activity, somewhat more pronounced on MCF-7 (breast carcinoma) and MOLT-4 (lymphoblastic leukemia) cells.
Horvat
Stefica
S
Division of Organic Chemistry and Biochemistry, Ruder Bosković Institute, Zagreb 10002-HR, Croatia. shorvat@irb.hr
Kralj
Marijeta
M
Perc
Milica
M
Jerić
Ivanka
I
Varga-Defterdarović
Lidija
L
Jakas
Andreja
A
Roscić
Maja
M
Suman
Lidija
L
Gredicak
Matija
M
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004745:Enkephalins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50
D000970:Antineoplastic Agents; D004745:Enkephalins