Synthesis of peptides analogous to the N-terminal eicosapeptide of ribonuclease A. Part IV. Synthesis of the enzymatically active Orn10 and Orn10, Glu11-eicosapeptides

Abstract

The syntheses of two analogous N-terminal eicosapeptides of the bovine pancreatic ribonuclease A, the Orn¹⁰-and the Orn¹⁰- Glu¹¹-S-peptides, are described.

N ^α N ^ε -Di-t-butoxycarbonyl-L-lysyl-γ-t-butyl-L-glutamyl-L-threonyl-L-alanyl-L-alanyl-L-alanine azide was condensed with N^ε-t-butoxycarbonyl-L-lysyl-L-phenylalanyl-γ-t-butyl-L-glutamyl-N^δ-t-butoxycarbonyl-L-ornithyl-L-glutaminyl-L-histidine methyl ester or with N^ε-t-butoxycarbonyl-L-lysyl-L-phenylalanyl-γ-t-butyl-L-glutamyl-N^δ-t-butoxycarbonyl-L-ornithyl-γ-t-butyl-L-glutamyl-L-histidine methyl ester. The hydrazides of the dodecapeptide esters were condensed, by an azide coupling step, with the C-terminal octapeptide, L-methionyl-L-aspartyl-L-seryl-L-seryl-L-threonyl-L-seryl-L-alanyl-L-alanine. The resulting eicosapeptides, after treatment with trifluoroacetic acid, were purified by chromatography on Amberlite C.G. 50, desalted on Sephadex G. 25 and lyophilised.

The synthetic peptides, after recombination with S-protein in different ratios, were able to restore 37–88% of the activity of the RNase S′, with yeast ribonucleic acid as substrate.