Synthesis of Tyrosine, Tryptophan and Methionine Peptides Using n-Formyl Protection and n,N '-Dicyclohexylcarbodiimide Coupling. Chromatographic Properties and Enzyme Susceptibilities

摘要

Using N-formyl protection and N, N'-dicyclohexylcarbodimide coupling, a simple, direct procedure is described for the incorporation of a variety of amino acids with reactive side chains into peptides. Included amongose synthesized were three series of peptides or peptide esters containing (1) up to five tyrosine residues, (2) up to four tryptophan residues, and (3) up to four methionine residues. The procedure consisted of coupling the N-formylamino acid to the amino acid ester by means of N,N'-dicyclohexylcarbodiimide. The resulting N-formyl peptide ester was deformylated with alcoholic hydrogen chloride and the product was neutralized to give the dipeptide ester. Successive repetitions of this procedure using the peptide ester and more N-formylamino acid progressively lengthened the peptide chain. Saponification of the peptide ester at any intermediate stage produced the corresponding free peptide. By means of crystalline enzymes the L-configuration was demonstrated for most, but not all, residues. For the most part, the susceptibilities of the peptides conformed with the known specificities of the enzymes. Variation of Rf with chain length was studied for each series of peptides in several different solvent systems. (Author)