MSP-1 malaria pseudopeptide analogs: biological and immunological significance and three-dimensional structure.
Merozoite Surface Protein-1 (MSP-1) has been considered as a malaria vaccine candidate. It is processed during the Plasmodium falciparum invasion process of red blood cells (RBCs). A conserved MSP-1 C-terminal peptide was identified as a high-activity erythrocyte-binding peptide (HAEBP) termed 1585. Since conserved HAEBPs are neither antigenic nor immunogenic we decided to assess the significance of a single peptide bond replacement in 1585. Thus, two pseudopeptides were obtained by introducing a Y[CH2-NH] reduced amide isoster into the 1585 critical binding motif. The pseudopeptides bound to different HLA-DR alleles, suggesting that backbone modifications affect MHC-II binding patterns. Pseudopeptide-antibodies inhibit in vitro parasite RBC invasion by recognizing MSP-1. Each pseudopeptide-induced antibody shows distinct recognition patterns. 1H-NMR studies demonstrated that isoster bonds modulate the pseudopeptides' structure and thus their immunological properties, therefore representing a possible subunit malaria vaccine component.
Lozano
José Manuel
JM
Fundación Instituto de Inmunología de Colombia, Carrera 50 No. 26-00, Bogotá, Colombia.
Alba
Martha Patricia
MP
Vanegas
Magnolia
M
Silva
Yolanda
Y
Torres-Castellanos
José Libardo
JL
Patarroyo
Manuel Elkin
ME
D000447:Aldehydes / Q000737:chemistry; D000577:Amides / Q000138:chemical synthesis; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000737:chemistry / Q000276:immunology; D002855:Chromatography, Thin Layer; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D009682:Magnetic Resonance Spectroscopy; D020066:Merozoite Surface Protein 1 / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000276:immunology*; D011485:Protein Binding; D011487:Protein Conformation; D012997:Solvents; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000447:Aldehydes; D000577:Amides; D000913:Antibodies, Protozoan; D006684:HLA-DR Antigens; D020066:Merozoite Surface Protein 1; D012997:Solvents