Mapping the anatomy of a Plasmodium falciparum MSP-1 epitope using pseudopeptide-induced mono- and polyclonal antibodies and CD and NMR conformation analysis

Journal of Structural Biology
José Manuel LozanoManuel Elkin Patarroyo

Abstract

Antigen structure modulation represents an approach towards designing subunit malaria vaccines. A specific epitope's alpha carbon stereochemistry, as well as its backbone topochemistry, was assessed for obtaining novel malarial immunogens. A variety of MSP-1(38-61) Plasmodium falciparum epitope pseudopeptides derived were synthesised, based on solid-phase pseudopeptide chemistry strategies; these included all-L, all-D, partially-D substituted, all-Psi-[NH-CO]-Retro, all-Psi-[NH-CO]-Retro-inverso, and Psi-[CH2NH] reduced amide surrogates. We demonstrate that specific recombinant MSP-1(34-469) fragment binding to red blood cells (RBCs) is specifically inhibited by non-modified MSP-1(42-61), as well as by its V52-L53, M51-V52 reduced amide surrogates and partial-D substitutions in K48 and E49. In vivo tests revealed that reduced amide pseudopeptide-immunised Aotus monkeys induced neutralising antibodies specifically recognising the MSP-1 N-terminus region. These findings support the role of molecular conformation in malaria vaccine development.

References

Aug 15, 1978·European Journal of Pharmacology·N W PedigoH I Yamamura
Jul 1, 1976·European Journal of Immunology·G Köhler, C Milstein
Dec 16, 1983·Biochemical and Biophysical Research Communications·M RanceK Wüthrich
Jan 9, 2001·Clinical Microbiology Reviews·R S Phillips
Aug 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Danilo RoccatanoAlan E Mark

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Citations

Apr 20, 2006·Journal of Computer-aided Molecular Design·David CurcóCarlos Alemán
Mar 9, 2005·Biochemical and Biophysical Research Communications·José Manuel LozanoManuel Elkin Patarroyo
Jan 9, 2007·Biochemical and Biophysical Research Communications·César SeguraVictor Lemeshko
Dec 13, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hernando CurtidorManuel E Patarroyo

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