Efficient binding of reduced peptide bond pseudopeptides to major histocompatibility complex class I molecule.

Reduced peptide bond pseudopeptide analogues have been examined for their ability to bind murine class I molecules of the major histocompatibility complex (MHC). Eight pseudopeptide analogues of an antigenic peptide derived from Plasmodium berghei (H-Ser252-Tyr-Ile-Pro-Ser-Ala-Glu-Lys-Ile260-OH) were obtained by systematically replacing one peptide 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-Kd class I molecule. The comparative results show that five analogues can efficiently mimic the parent peptide while the introduction of the reduced bond between P3-P4, P7-P8, and P8-P9 is deleterious for SC-Kd binding. The fact that more stable pseudopeptides containing reduced peptide bonds can bind major histocompatibility complex molecules is of great interest for the design of peptidomimetics with potential therapeutical properties. Such peptide analogues may prove useful for the development of peptide-based cytotoxic T lymphocyte vaccines.