Stepwise transformation of a cholera toxin and a p24 (HIV-1) epitope into D-peptide analogs

We have transformed two peptide epitopes into D-peptide analogs: VPGSQHIDS derived from cholera toxin recognized by the antibody TE33, and GATPQDLNTML from the HIV-1 capsid protein p24 recognized by the antibody CB4-1. The transformation process was performed by stepwise substitution of each single...

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Veröffentlicht in:Protein engineering 1998-10, Vol.11 (10), p.941-948
Hauptverfasser: Kramer, A, Stigler, R D, Knaute, T, Hoffmann, B, Schneider-Mergener, J
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Sprache:eng
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Zusammenfassung:We have transformed two peptide epitopes into D-peptide analogs: VPGSQHIDS derived from cholera toxin recognized by the antibody TE33, and GATPQDLNTML from the HIV-1 capsid protein p24 recognized by the antibody CB4-1. The transformation process was performed by stepwise substitution of each single epitope position by all 19 D-amino acids and glycine followed by antibody binding studies and selection of one D-analog for further transformation. Thus, each transformation step introduced one novel D-position into the peptide. For both epitopes complete D-analogs were obtained. The cholera toxin-derived variant dwGsqhydp binds to the antibody TE33 with higher affinity than its original epitope, whereas in the case of the p24-derived analog saGdwwGkssl lower affinity was detected. Both D-peptides are completely stable in serum for several days. Antibody interaction models for both D-molecules were generated by computer-assisted modelling based on the crystal structures of the starting complexes. Compared with the L-peptides, the binding conformation of dwGsqhydp is very similar, whereas saGdwwGkssl displays a completely different interaction mode.
ISSN:0269-2139
1741-0126
1741-0134
DOI:10.1093/protein/11.10.941