Multicyclic Peptides Synthesized Using the Kaiser Oxime Resin: Helix Stabilizing Effects of Lactam Bridges,

The p-nitrobenzophenone oxime resin is useful for the preparation, in their fully protected forms and in high yield and purity, of cyclic peptides and peptides incorporating lactam-bridged side chains. With appropriate N sup alpha - and C sup alpha - connection, the lactam-bridged peptides have been used to prepare multicyclic peptides by segment-condensation synthesis. In combination with FMOC and OFm side-chain protection, we have also recently achieved the oxime resin-based synthesis of a protected peptide having two overlapping lactam bridges. Thus, the synthetic intermediate necessary for the construction of almost any type of multicyclic, lactam-bridged peptide may be prepared by this method. Such structures should be useful for determining the functional conformations of biologically active peptides, and enhancing their potencies, specificities and resistance to proteolysis.