Peptides terminally blocked dipeptide

Figure 1 Charge sensitivities of the free energy of a solution of glycine dipeptide in methanol. The first three atoms/extended atoms (CMl, C, and O) builds up the acetyl N-terminal blocking group. The next five atoms/extended atoms (N, H, CA, C, and O) represent components of a glycine unit. The last three atoms/extended atoms at the C-terminal end (N, H, and CM2) terminate the peptide as an N-methyl amide.

In the existing know-how of the field of peptide synthesis only limited guidance could be found and designing a scheme for the synthesis of oxytocin was a major challenge. No similar undertaking had been published up till then. Peptides obtained by synthesis were either much smaller or of fairly simple amino acid composition. Yet, the partially blocked dipeptide N-benzyloxycarbonyl-5-benzyl-L-cysteinyl-L-tyrosine, the N-terminal sequence, had already been pre-... 

The literature data on the preparation of phosphono-dipeptides from 1-aminoalkanephosphonic acids showed 7-7 that the yields of condensation reactions are usually small or moderate. Moreover,the use of bulky N-blocked amino acids drastically decreased the reaction yield. Thus following Martell s method— we wre unsuccesful in the preparation of dipeptides containing N-terminal valine or leucine,while peptides of phenylalanine were obtained in 5—10% yield.Also the active ester method appeared to give small yields of the desired products. Our studies using p-nitrophenyl- and cyanomethyl esters of N-phtaloyl amino acids confirmed these observations. 

---