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: VPGSQ HIDS derived from cholera toxin recognized by the antibody TE33, and G ATPQDLNTML from the HIV-1 capsid protein p24 recognized by the antibod y CB4-1, The transformation process was performed by stepwise substitu tion of each single epitope position by all 19 D-amino acids and glyci ne 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-an alogs 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 affini ty was detected. Both D-peptides are completely stable in;serum for se veral days. Antibody interaction models for both D-molecules were gene rated by computer-assisted modelling based on the crystal structures o f the starting complexes. Compared with the L-peptides, the binding co nformation of dwGsqhydp is very similar, whereas saGdwwGkssl displays a completely different interaction mode.