Reduced amide pseudopeptide analogues of a malaria peptide possess secondary structural elements responsible for induction of functional antibodies which react with native proteins expressed in Plasmodium falciparum erythrocyte stages
| Autor: | Julio C. Calvo, Fabiola Espejo, Luz Mary Salazar, Manuel E. Patarroyo, C. Pinzón, Diana Diaz, J. J. Rodríguez, Fanny Guzman, José Manuel Lozano |
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| Rok vydání: | 2009 |
| Předmět: |
Models
Molecular Peptide Biosynthesis Erythrocytes Magnetic Resonance Spectroscopy Molecular model Peptidomimetic medicine.drug_class Immunoblotting Plasmodium falciparum Antiprotozoal Agents Antibodies Protozoan Enzyme-Linked Immunosorbent Assay Peptide Biology Monoclonal antibody Biochemistry Mass Spectrometry Protein Structure Secondary Mice Endocrinology Malaria Vaccines parasitic diseases medicine Animals Peptide bond Immunization Schedule chemistry.chemical_classification Mice Inbred BALB C Malaria vaccine biology.organism_classification Amides Malaria Protein Structure Tertiary chemistry Female Chromatography Thin Layer Spleen Chromatography Liquid |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1397-002X |
| DOI: | 10.1111/j.1399-3011.1998.tb01250.x |
| Popis: | A psi[CH2NH] isoster bond was introduced by replacing one peptide bond at a time within the 1513 malaria peptide KEKMV motif to obtain a set of five pseudopeptides. The motif belongs to a Plasmodium falciparum malarial peptide coded 1513, derived from the MSP-1 protein. This high-binding motif included in the 1513 peptide is involved in the attachment of the malarial parasite to human erythrocytes. The novel malaria 1513 psi[CH2NH] surrogates were analyzed using RP-HPLC and MALDI-TOF mass spectrometry techniques. Nuclear magnetic resonance experiments allowed definition of the five pseudopeptide analogues' secondary structural features. Such structures are present in only a very few molecules in the 1513 parent peptide. A molecular model demonstrating the solution of the three-dimensional structure of the 1 513 peptide Pse-437 analogue was constructed on the basis of 1H-NMR spectral parameters. Monoclonal antibodies were generated to the five 1513 malaria peptide pseudopeptide analogues. These antibodies not only recognize the native MSP-1 (195 kDa) and its 83 kDa and 42 kDa proteolytic processing proteins but also different SPf(66)n malaria vaccine batches containing the native sequence. In addition, the mAbs were able to modify the kinetics of Plasmodium falciparum parasites' intraerythrocytic development and their ability to invade new RBCs. The presented evidence suggests that peptide bond-modified peptides could reproduce a transient state in 1513's native sequence and represent useful candidates in the development of a second generation of effective malarial vaccines. |
| Databáze: | OpenAIRE |
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