We are focusing our effects on developing the synthesis of protected peptide fragments on solid supports using amino acid esters of oximes as the anchoring groups. We have shown that peptides can be assembled on polymer-bound p-nitroenzophenone oxime, for instance, employing conditions analogous to those customarily used in the Merrifield stepwise approach and that protected peptide fragments can be removed from the polymer by mild treatment with hydrazine, N,N-diethylhydroxylamine or glycine ethyl and t-butyl esters. We intend to use the protected fragments obtained, containing C-terminal hydrazine, carboxylic acid or ester functions, in the synthesis of larger peptides. Thus, it should be possible to convert the hydrazides to azides further coupling of the fragments or to use oxidation-reduction condensation for coupling the protected peptides with C-terminal carboxylic acid groups to suitable N-protected peptide fragments. Development of the polymer-bound oxime ester method should enable us to synthesize peptides containing up to 50-60 amino acids by a combination of fragment synthesis and condensation. Since this approach should aid the preparation of polypeptides having single amino acid replacements in crucial regions, synthetic studies of structure-activity relationships for a variety of rather large biologically important peptides should be facilitated. We are completing studies on the synthesis of a truncated model of pancreatic trypsin inhibitor (Kunitz) and we have undertaken the preparation of a model peptide (twenty-six amino acids in length) designed to behave like a bee venom toxin melittin. In our further research we expect to prepare a number of new derivatives to be submitted to the National Cancer Institute's anti-tumor screening program.