DNA-binding and Oxidative Properties of Cationic Phthalocyanines and Their Dimeric Complexes with Anionic Phthalocyanines Covalently Linked to Oligonucleotides

Abstract

Design of chemically modified oligonucleotides for regulation of gene expression has attracted considerable attention over the past decades. One actively pursued approach involves antisense or antigene oligonucleotide constructs carrying reactive groups, many of these based on transition metal complexes. The complexes of Fe(II) and Co(II) with phthalocyanines are extremely good catalysts of oxidation of organic compounds with molecular oxygen and hydrogen peroxide. The binding of positively charged Fe(II) and Co(II) phthalocyanines with single- and double-stranded DNA was investigated. It was shown that these phthalocyanines interact with nucleic acids through an outside binding mode. The site-directed modification of single-stranded DNA by O₂ and H₂O₂ in the presence of dimeric complexes of negatively and positively charged Fe(II) and Co(II) phthalocyanines was investigated. These complexes were formed directly on single-stranded DNA through interaction between negatively charged phthalocyanine in conjugate and positively charged phthalocyanine in solution. The resulting oppositely charged phthalocyanine complexes showed significant increase of catalytic activity compared with monomeric forms of phthalocyanines Fe(II) and Co(II). These complexes catalyzed the DNA oxidation with high efficacy and led to direct DNA strand cleavage. It was determined that oxidation of DNA by molecular oxygen catalyzed by complex of Fe(II)-phthalocyanines proceeds with higher rate than in the case of Co(II)-phthalocyanines but the latter led to a greater extent of target DNA modification.     

Evolution of catalytic centers of antibodies by virtual screening of broad repertoire of mutants using supercomputer

It is proposed to perform quantum mechanical/molecular dynamics calculations of chemical reactions that are planned to be catalyzed by antibodies and then conduct a virtual screening of the library of potential antibody mutants to select an optimal biocatalyst. We tested the effectiveness of this approach by the example of hydrolysis of organophosphorus toxicant paraoxon using kinetic approaches and X-ray analysis of the antibody biocatalyst designed de novo.     

Reactive derivative of adenosine-5′-triphosphate formed by irradiation of ATP γ-p-azidoanilide

UV and ¹H NMR spectra changes demonstrate that p-azidoanilides of ATP, ITP, pyrophosphate after irradiation at 313 nm, transform to similar reactive intermediates. The latter react readily with morpholine, iso-propylamine, tert-butylamine, imidazole, mercaptoethanol the reactivity being qualitatively correlated with nucleophilicity. By analogy with the transformation of p-azidoanilide, it is concluded that the reactive intermediate is the respective derivative of quinone diimine. Photoaffinity labelling of proteins with p-azidoanilide derivatives may proceed as the reaction of the nucleophilic centers of proteins with this quinone diimine derivative, rather than as a direct attack by a nitrene biradical.