Solid phase synthesis of a redox delivery system with the aim of targeting peptides into the brain

A solid phase approach for the preparation of peptides attached to a redox chemical delivery system derived from stable annulated NADH models is reported. The synthesis starts with the grafting on a Merrifield resin of quinoline 4b, precursor of the redox carrier. From the resulting quinoline supported resin 4d, the stepwise SPPS of both octapeptide OP (RPGLLDLK) and octadecaneuropeptide ODN (QATVGDVNTDRPGLLDLK), two neuropeptides exhibiting anorexigenic effects, was successfully achieved by conventional methods. Quaternization of the quinoline moiety prior to cleavage of the modified OP and ODN peptides from the resin, led to the expected quinolinium salt 8a and 8b respectively linked to OP or ODN peptides. Finally, the reduction with NaBH4 monitored by UV-vis, provided the desired annulated NADH models as peptides carriers with either the OP (11a,b) or ODN (12a,b) moiety.