Alkylation of nucleic acid components by ethyleneimine derivatives. I. Alkylation of bases

In the course of investigating the reaction conditions of the nucleic acid components alcylation, the interaction of thioTEPA (N,N',N'-triethylenethiophosphoamide) with hydrochloric and perchloric acids was studied, perchloric acid increasing the alkylation products yield. HPLC and UV spectroscopy were used to isolate and identify products of nucleic bases alkylation by ethylenimine and its derivatives (thioTEPA and monoaziridinediethylphosphate). It is shown that under neutral conditions phosphoaminoethylation takes place, whereas under slightly acidic conditions products of aminoethylation are formed.     

Alkylation of DNA and its aftermath

Current pharmacopoeias invariably refer to a category of ‘alkylating drugs’, still among the most widely used in cancer chemotherapy. They are described as acting through their ability to damage DNA, thus interfering with cell replication. Unfortunately, this mode of action implicates these drugs as carcinogens. Thus the early studies recalled in this essay proved to be relevant to our understanding of both the main problems with which cancer research concerns itself: the causation of cancer and possible methods of treatment of this group of diseases.     

Isopoly(S-carboxymethyl-L-cysteine) derivatives of nucleic acid bases: effects of D-cysteine derivatives on the interaction with DNA.

Isopoly(S-carboxymethyl-D-cysteine) derivatives of nucleic acid bases were prepared to study the effect of chirality on the complex formation with oligo-DNA. The D-cysteine unit in the L-cysteine oligomer caused decrease of Tm for the complex with DNA.     

Watersoluble synthetic nucleic acid analogs--polyethyleneimine derivatives containing nucleic acid bases--conformation and interactionwith nucleic acids

Water soluble polyethyleneimine derivatives containing nucleic acid bases were found to interact with polynucleotides, DNA, RNA. The conformational change by formation of complex was observed by CD spectra and was discussed with the hypochromicity in UV spectra. The rates of interactions between nucleic acid bases in polymers were slow as shown by UV spectra, but the conformational changes of the polynucleotides were fast as shown by CD spectra. In the case of the uracil derivative (PEI-Hse-Ura), high value of CD spectra [theta] 2.80 = -8.0 x 10(-4) for the complex with DNA might be caused by psi type conformation of DNA.     

Affinity chromatography of nucleosides and nucleic acid base derivatives with nucleic acid bases or nitrobenzeneboronic acid substituted silicas

Nucleic acid bases such as adenine and uracil, and nitrobenzeneboronic acid substituted silicas were prepared by the reaction of chloromethylbenzene substituted silica with adenine sodium salt and trimethylsilylated uracil, and nitration of benzeneboronic acid substituted silica, respectively. From the results of HPLC of nucleosides and N-ethyl derivatives of nucleic acid bases using modified silicas, hydrophobic base stacking interaction, selective hydrogen bonding interaction between purine and pyrimidine bases, and reversible cyclic boronate ester formation between diols of nucleosides with boronic acid were effective for the separation of nucleic acid related compounds. Moreover, association constants for hydrogen bonding formation of nucleic acid bases were estimated.     

Definitions and nomenclature of nucleic acid structure components

We report here recommendations for the definitions and nomenclature of nucleic acid structure parameters. These recommendations result from discussions at an EMBO Workshop on DNA Curvature and Bending held at Churchill College, Cambridge, in September 1988.