Pentopyranosyl Oligonucleotide Systems. 9th Communication

Pyranosyl‐RNA (‘p‐RNA’ ) is an oligonucleotide system isomeric to natural RNA and composed of the very same building blocks as RNA. Its generational, chemical, and informational properties are deemed to be those of an alternative nucleic acid system that could have been a candidate in Nature's evolutionary choice of the molecular basis of genetic function. We consider the study of the chemistry of p‐RNA as etiologically relevant in the sense that knowledge of its structural, chemical, and informational properties on the chemical level offers both a perspective and reference points for the recognition of specific structural assets of the RNA structure that made it the (supposedly) superior system among possible alternatives and, therefore, the system that became part of biology as we know it today. The paper describes the chemical synthesis of β‐d‐ (and L )‐ribopyranosyl‐(4′→2′)‐oligonucleotide sequences, presents a resume of their structural and chemical properties, and cautiously discusses what we may and may not have learned from the pyranosyl isomer of RNA with respect to the conundrum of RNA's origin.     

Current methods for site-directed structure generation

Summary There has been a rapid growth of interest in techniques for site-directed drug design, fuelled by the increasing availability of structural models of proteins of therapeutic importance, and by studies reported in the literature showing that potent chemical leads can be obtained by these techniques. Structure generation programs offer the prospect of discovering highly original lead structures from novel chemical families. Due to the fact that this technique is more-or-less still in its infancy, there are no case studies available that demonstrate the use of structure generation programs for site-directed drug design. Such programs were first proposed in 1986, and became commercially available in early 1992. They have shown their ability to reproduce, or suggest reasonable alternatives for, ligands in well-defined binding sites. This brief review will discuss the recent advances that have been made in the field of site-directed structure generation.     

Robust Adaptive Identification of Fuzzy Systems with Uncertain Data

This study presents a method of adaptive identification of parameters describing Sugeno fuzzy inference system in presence of bounded disturbances while maintaining the readability and interpretability of the fuzzy model during and after identification. This method do not require any a priori knowledge of a bound on the disturbance and noise and of a bound on the unknown parameters values. The method can be used for the robust and adaptive identification of slowly time varying nonlinear systems using fuzzy inference systems. The suggested method was used to build a fuzzy expert system that approximates the functional relationship between physical fitness and some of the measurable physiological parameters by their real measurements and opinion (human-experiences) of a medical expert.     

Nucleosides and Nucleotides. Part 21. Synthesis of a Tridecanucleoside Dodecaphosphate Incorporating the Unnatural Base 2 (1 H)-Pyridone

The modified nucleoside Π_d (1) was used in the synthesis of the oligonucleotide d (TpTpΠpCpGpTpCpApApApApTpC). Diester methodology being unsatisfactory, the triester synthesis was investigated with the unnatural nucleoside. An improved method of nucleoside phosphorylation was developed for the synthesis of the fully-protected nucleotide 2e. This molecule could be cleanly and selectively deprotected, and allowed the efficient synthesis of the desired oligonucleotide.     

OXYGEN QUENCHING IN MICELLAR SOLUTION AND ITS EFFECT ON THE PHOTOCYCLIZATION OF N-METHYLDIPHENYLAMINE

Abstract— Oxygen effects on the photocyclization of N-methyldiphenylamine to N-methylcarbazole were investigated in n-hexane, water, and aqueous surfactant solutions by steady state irradiations and flash photolysis measurements. The reaction sequence in micelles was found to involve the same intermediate steps as in homogeneous solutions. In aerated micellar solutions, the quantum yield of N-methylcarbazole is significantly higher than in n-hexane, while the rate constants of the unimolecular reaction steps show no solvent dependence. The bimolecular dehydrogenation of the intermediate 4a, 4b-dihydro-N-methylcarbazole by oxygen is enhanced in aqueous and micellar solutions, whereas the quenching rate of triplet intermediates by oxygen was not affected. The lesuhs are interpreted using a dispersed phase model of micellar solutions. Special 'micellar effects' need not be invoked since the dependence of the quantum yield on the solvent is shown to be due to the difference in the overall oxygen concentration.