1H‐nmr studies of synthetic polypeptide models of Plasmodium falciparum circumsporozoite protein tandemly repeated sequence

Abstract

The major immunodominant region of the coating protein of Plasmodium falciparum sporozoites contains multiple tandem copies of the sequence Asn-Ala-Asn-Pro (NANP). Current efforts for the development of an antisporozoite vaccine are focused on the synthesis of polypeptides reproducing part of the circumsporozoite protein repeat sequence and, in an attempt to relate conformational properties and biological response, ¹H-nmr one- and two-dimensional studies of the synthetic models (NANP)₂NA and (NANP)₆ were carried out in water and water/methanol mixtures, at 400 and 500 MHz. In water, (NANP)₆ undergoes fast conformational averaging. At variance, in water/methanol, the molecule appears to adopt an extensive structure, but detailed analysis is impaired by high spectral degeneracy. Based on the results obtained with (NANP)₂NA and from preliminary expermints in water/trifluoroethanol, an interpretation is suggested for the (NANP)₆ data in water/methanol in terms of a mixed sequence of βI-turns and half-turns (or/and γ_I-turns) around the positions N_i−1-P_i-N_i+1.