Ribonuclease Activity of the Peptides with Alternating Arginine and Leucine Residues Conjugated to Tetrathymidilate

Abstract

RNA cleaving conjugates have been prepared by attachment of oligodeoxyribonucleotide TTTT to peptides containing arginine, leucine, proline and serine residues. The highest activity was displayed by the conjugates containing peptides with alternating arginine and leucine residues (LR)₄G‐amide. Ribonuclease activity of the conjugates pep‐T₄ decreases in the order T₄‐(LR)₄G > T₄‐(LR)₂G > T₄‐(LLRR)2G > T₄‐(LR)₂PRLRG > S₂R₃‐Hmda‐T₄ ≥ R₅ ≠ (LR)₃. According to CD spectra, the free peptide (LR)₄G‐amide in water solution at neutral pH and physiological ionic strength has no pronounced secondary structure whereas conjugated to oligonucleotide it acquires a folding similar to α‐helix.

Keywords:

• Artificial ribonucleases
• Oligonucleotide‐peptide conjugates

Acknowledgments

This work was supported by the grants from The Wellcome Trust (No. 063630), CRDF NO‐008‐X1 and a grant from the Ministry of Education of the Russian Federation under the auspices of the program “Fundamental investigations and high education” Y1‐B‐08‐08, RFBR No. 02‐04‐48664 and 03‐04‐06238, grant SS‐1384.2003.4, grant SB RAS for Interdisciplinary investigations and in Support of young scientists.