Use of sequential oligopeptide carriers (SOCn) in the design of potent Leishmania gp63 immunogenic peptides.
The antigenic sequence Ac-IASRYDQL (gp63-SRYD) of the major surface glycoprotein of Leishmania, gp63, was covalently attached to the Lys-N epsilon H2 groups of a new sequential oligopeptide carrier (SOCn), namely, (Lys-Aib-Gly)n (n = 5.6), in order to obtain potent immunogens and site-specific antibodies. It was shown, using 1H-NMR spectroscopy, that the gp63-SRYD octapeptides bound to the SOCn retain their original structural profile outlined by an ionic interaction between R and D side chains and a type 1 beta-turn involving the QNH-->RCO hydrogen bonding. Also, the gp63-SRYD octapeptides linked to the carrier do not experience conformational restrictions, probably because of the favorable conformation of the SOCn. Immunizations of outbred rabbits with the peptide carriers designed resulted in high-titered antibody response to the gp63-SRYD octapeptide and the gp63 cognate protein. Thus, this chemically defined model may be used for incorporating "protective" Leishmania epitopes and ultimately for the design of a multivalent synthetic vaccine against leishmaniosis.
Tsikaris
V
V
Department of Chemistry, University of Ioannina, Greece.
Sakarellos
C
C
Sakarellos-Daitsiotis
M
M
Cung
M T
MT
Marraud
M
M
Konidou
G
G
Tzinia
A
A
Soteriadou
K P
KP
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D004337:Drug Carriers / Q000737:chemistry; D015195:Drug Design; D007114:Immunization; D007891:Leishmania / Q000276:immunology*; D009682:Magnetic Resonance Spectroscopy; D008666:Metalloendopeptidases / Q000737:chemistry / Q000276:immunology*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology*; D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D004337:Drug Carriers; D009842:Oligopeptides; D010446:Peptide Fragments; D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic; D008666:Metalloendopeptidases; C055146:glycoprotein gp63, Leishmania