Artificial ribonucleases 5. Synthesis and ribonuclease activity of tripeptides composed of amino acids involved in catalytic centers of natural ribonucleases

The characteristic features of the spatial arrangement of the main functional groups involved in catalytic centers of ribonucleases and nucleases were revealed by computer analysis of the catalytic centers of these enzymes. Based on the results of computer simulation, tripeptides containing Lys, Arg, His or Hia, Thr, and Asn in different combinations were synthesized. In these tripeptides, the distances between the corresponding functional groups are equal to those observed in natural enzymes. The efficacy of RNA cleavage with Arg- and His-containing tripeptides depends on their structure and correlates with the overall positive charge of these compounds. Of all the tripeptides under consideration, compounds bearing the overall charge of +4 exhibit the highest ribonuclease activity.