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

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 p seudopeptides. The motif belongs to a Plasmodium falciparum malarial peptid e coded 1513, derived from the MSP-1 protein. This high-binding motif inclu ded in the 1513 peptide is involved in the attachment of the malarial paras ite to human erythrocytes. The novel malaria 1513 Psi[CH2NH] surrogates wer e analyzed using RP-HPLC and MALDI-TOF mass spectrometry techniques. Nuclear magnetic resonance experiments allowed definition of the five pseud opeptide analogues' secondary structural features. Such structures are pres ent in only a very few molecules in the 1513 parent peptide. A molecular mo del demonstrating the solution of the three-dimensional structure of the 15 13 peptide Pse-437 analogue was constructed on the basis of H-1-NMR spectra l parameters. Monoclonal antibodies were generated to the five 1513 malaria peptide pseud opeptide analogues. These antibodies not only recognize the native MSP-1 (1 95 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 falcip arum parasites' intraerythrocytic development and their ability to invade n ew RBCs. The presented evidence suggests that peptide bond-modified peptides could r eproduce a transient state in 1513's native sequence and represent useful c andidates in the development of a second generation of effective malarial v accines.