Synthesis of new P3CS derivatives and their mitogenic activity on in vitro mice splenocytes.
Vaccination against tumors represents a relevant issue in current human cancer therapy. The N-terminal part of the lipoprotein from the outer membrane of Escherichia coli, tripalmitoyl-S-glyceryl-Cys-Ser (P(3)CS) and analogs with longer aminoacidic sequence are polyclonal activators for B-lymphocytes. Previous study reported that their N-2,2,2-trichloroethoxycarbonyl (Troc) derivatives increase immunocyte mitogenic activity. Therefore, in order to obtain compounds of greater activity and to investigate relationships between molecular structure of S-glyceryl skeleton and biological activity, we synthesized new Troc derivatives of P(3)CS. The mitogenicity of compounds was determined in vitro, by measuring in vitro [3H]-thymidine incorporation into splenocytes from Balb/c mice. Concentrations of compounds ranged from 0 to 64 micro g/ml. In particular, S-[2,3-bis(trichloroethoxycarbonyloxy)]-N-trichloroethoxycarbonyl dipeptide derivative exhibited significant mitogenic activity endowed with high pharmacological potency. These new series of compounds could be used as potent immunoadjuvants for the development of novel synthetic vaccines for tumor immunotherapy.
Pappalardo
Maria
M
Department of Pharmaceutical Science, School of Pharmacy, School of Medicine, University of Catania, Viale Andrea 6, 95125, Catania, Italy. mrspld@mbox.unict.it
Bousquet
Ennio
E
Annino
Agata
A
Lombardo
Gabriella
G
Bernardini
Renato
R
Ronsisvalle
Giuseppe
G
D000818:Animals; D002478:Cells, Cultured; D004151:Dipeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008934:Mitogens / Q000138:chemical synthesis / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects*
D004151:Dipeptides; D008074:Lipoproteins; D008934:Mitogens; C047210:2,3-bis-(palmitoyloxy)-2-propyl-N-palmitoyl-cysteinylserine