Sequential polypeptides. Synthesis of poly-(L-tyrosyl-L-glutamyl-L-tyrosyl-L-glutamyl), poly-(L-glutamyl-L-tyrosyl-L-glutamyl), and poly-(L-glutamyl-L-glutamyl-L-tyrosyl-L-glutamyl) by use of catechol esters

Abstract

The racemization-free method of peptide coupling involving use of 2-hydroxyphenyl esters has been successfully applied to the synthesis of sequential polypeptides containing L-tyrosine and L-glutamic acid. The reactive hydroxy-group of these esters was protected by formation of a phenacyl ether; this led to easily crystallizable derivatives, and the protective group could be removed selectively with zinc dust in acetic acid. The benzyl group was used to protect side-chains of tyrosine and glutamic acid. It was removed by use of a saturated solution of hydrogen bromide in acetic acid; use of the equivalent hydrogen bromide–trifluoroacetic acid mixture leads to irreversible modification of tyrosine. Kinetic measurements have shown that rates of aminolysis are highly dependent on the concentration of triethylamine. Molecular weights of deprotected polypeptides were in most cases around 10,000.