SYNTHESIS OF PEPTIDE ANALOGS OF THE N‐TERMINAL EICOSAPEPTIDE SEQUENCE OF RIBONUCLEASE A.

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Abstract
Synthesis of the S‐peptide analog in which the arginyl residue in position 10 and the histidyl residue in position 12 are simultaneously replaced by two ornithines is described. The stereochemical homogeneity of the [Orn 10, Orn 12]‐S‐peptide has been assessed by digestion with aminopeptidase M. The ability of the synthetic S‐peptide analog to bind and to activate S‐protein was tested, before and after guanidination, by exploring its capacity to compete with S‐peptide for S‐protein and to generate ribonuclease activity when recombined with S‐protein.The binding capacity of the synthetic material has been also evaluated by differential spectroscopy. Both the examined products failed to activate S‐protein at a molar ratio as high as 500:1 with RNA, cytidine 2′, 3′‐cyclic phosphate, and cytidylyl (3′‐5′) cytidine as substrate. Moreover, inhibition studies and spectrophotometric measurements showed that the synthetic S‐peptide analog as well as its guanidinated derivative are also unable to bind to S‐protein. It seems that the histidyl residue in position 12 in the S‐peptide sequence, in addition to the critical role played in the catalytic function, should be also important in the association process between S‐peptide and S‐protein.