EFFICIENT BINDING OF REDUCED PEPTIDE-BOND PSEUDOPEPTIDES TO MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULE

Reduced peptide bond pseudopeptide analogues have been examined for th eir ability to bind murine class I molecules of the major histocompati bility complex (MHC), Eight pseudopeptide analogues of an antigenic pe ptide derived from Plasmodium berghei -Ser(252)-Tyr-Ile-Pro-Ser-Ala-Gl u-Lys-Ile(260)-OH) were obtained by systematically replacing one pepti de bond at a time by a reduced peptide bond Psi(CH2-NH). The resulting analogues Were then tested for their binding to a recombinant single chain SC-K-d class I molecule. The comparative results show that five analogues can efficiently mimic the parent peptide while the introduct ion of the reduced bond between P3-P4, P7-P8, and P8-P9 is deleterious for SC-K-d binding, The fact that more stable pseudopeptides containi ng reduced peptide bonds can bind major histocompatibility complex mol ecules is of great interest for the design of peptidomimetics with pot ential therapeutical properties. Such peptide analogues may prove usef ul for the development of peptide-based cytotoxic T lymphocyte vaccine s.