![]() Book of Abstracts: Albany 2009![]() Conversation 16 June 16-20 2009 © Adenine Press (2008) Structural Aspects of Oligonucleotide-mediated Artificial RibonucleasesThe development of novel biocatalytic supramolecular structures mimicking the active center of natural ribonucleases and capable of cleaving RNA targets can provide a basis for generating new useful biological tools and powerful therapeutics, affecting specific messenger RNAs and viral genomic RNAs. Recently, a new type of chemical nuclease (1-4), showing very unusual catalytic and structural properties, was discovered. These novel oligonucleotide-mediated chemical nucleases were constructed by chemical conjugation of short, catalytically inactive oligopeptides containing alternating basic and hydrophobic amino acids with an oligonucleotide component (1-4). The most remarkable feature of these novel biocatalysts was that the conjugation of peptide and oligonucleotide seems to produce a new, hybrid type of molecule that can synergistically combine the individual properties of the two components to yield a new and unusual catalytic ability.
In this research we present structural aspects of a new type of catalytic artificial ribonucleases with high catalytic turnover and efficiency, using 2D NMR spectroscopy and molecular modelling. Our structural studies of these oligonucleotide-mediated chemical nucleases revealed a clear Structure-Function correlation in terms of their ability to cleave single-stranded regions of an RNA target. Spectroscopic and computational data obtained so far provides sufficient evidence that both oligonucleotide and peptide cross-modulate each other?s conformations leading to a formation of a new entity with unique structural and functional properties. The oligonucleotide component seems to induce an `active' conformation of the peptide and hence significantly enhance its catalytic performance. The manipulation of the structural properties of these catalytic nucleases may lead to a creation of new types of synthetic ribonucleases of high activity and desired base-specificity. References and Footnotes
Steven M. Miles1 1School of Pharmacy |