KINETIC AND CONFORMATIONAL STUDIES ON SOME PARTIALLY SYNTHETIC RIBONUCLEASE S‘ ANALOGUES MODIFIED IN POSITION 8*

Abstract
Syntheses are described of two S‐peptide analogues where the arginyl residue in position 10 has been replaced by ornithine and the phenylalanine in position 8 has been substituted by the unnatural amino acids cyclohexylalanine or p‐fluorophenylalanine.In order to regenerate the arginyl residue, which is present in position 10 in the natural sequence, the S‐peptide analogues belonging to the [Orn10]‐series are transformed into the corresponding guanidinated derivatives by treatment with O‐methylisourea. 1∈, 7∈, 10δ triguan‐[Cha8, Orn10]‐, 1∈, 7∈, 10δ‐triguan‐[pF‐Phe8, Orn10]‐ and 1∈, 7∈, 10δ‐triguan‐[Tyr8, Orn10]‐S‐peptides were prepared.The ability to bind to and activate the S‐protein of the synthetic S‐peptide analogues, before and after guanidination, was tested by exploring their capacity to generate ribonuclease activity using RNA and C > p as substrates.The affinity of the different peptides for the S‐protein in the absence of substrate was evaluated by difference spectroscopy.

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