Clinton F. Ainsworth

Synthesis of Deoxyribonucleotidyl (3′-5′) Arabinonucleosides

Abstract Two different synthetic routes using phosphotriester methodology have been utilized to prepare deoxyribonucleotidyl (3′–5′) arabinonucleosides containing 9-β-D-arabinofuranosyladenine (ara-A, vidarabine) and 1-β-D-arabinofuranosylcytosine (ara-C, cytarabine) at the 3′-terminus in amounts and purity (greater than 95%) suitable for NMR analysis.

NMR Investigations of the Solution Conformations of Deoxynucleotidyl (3′-5′) Arabinonucleosides

Abstract The solution conformations of all eight deoxynucleotidyl (3′-5′) arabinonucleosides containing 9-B-D-arabinofuranosyladenine and 1-B-D-arabinonfuranosylcytosine have been analyzed by NMR methods and compared to dinucleoside monophosphates containing the corresponding deoxyriboside units.

METHYLATION EFFECTS ON NUCLEIC ACID CONFORMATIONS

Chemical modification of nucleic acids by alkylating agents continues to be extensively explored from the perspective of chemical mutagenesis and carcinogenesis. Largely through the pioneering in vitro and in vivo studies of Lawley (1961), Lawley and Brookes (1963), Singer (1972), and Reese and coworkers (1965), coupled with theoretical predictions of Pullman (1974), a detailed profile has emerged of the principal alkylation sites for purine and pyrimidine nucleotides. Generally, alkylation of nucleic acids produces a multiplicity of reaction products dependent upon factors such as nature of base ring, electrophilicity of the alkylating agent (Lawley, 1976), and presence of activating enzymes (Magee and Barnes, 1967). Thus, for example, alklation of adenine nucleotides can occur at six sites, Figure 1. Strong electrophiles such as N-methyl-N-nitrosourea (MNUA) and N-methyl-N1-nitro-N-nitrosoguani-dine (MNNG) couple preferentially with available oxygen donors, e.g., phosphate group, 2′ oxygen in ribonucleotides, while weakly electrophilic agents dimethyl sulfate and methyl methane sulfonate tend to show a higher proportion of ring nitrogen methylation at N1, N3, and N7 of purines.