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1, N (2)-Propanodeoxyguanosine (PdG) is a stable structural analogue for the 3-(2'-deoxy-beta- d- erythro-pentofuranosyl)pyrimido[1,2-alpha]purin-10(3 H)-one (M 1dG) adduct derived from exposure of DNA to base propenals and to malondialdehyde. The structures of ternary polymerase-DNA-dNTP complexes for three template-primer DNA sequences were determined,(More)
The production of a milk-clotting enzyme by Aspergillus versicolor in 19 different culture media was investigated. Considerable milk-clotting activity was achieved by supplying corn steep liquor with either glucose of maltose. Dephytinization of corn steep liquor had an adverse effect on the production of milk-clotting enzyme. The results indicated that(More)
From the whole plants of Euphorbia petiolata, four new ingenane-type diterpenoids, 3,20-O-diacetylingenol 5-O-(2' E,4' Z)-tetradecadienoate (1), 5,20-O-diacetylingenol 3- O-(2' E,4' Z)-tetradecadienoate (2), ingenol 3-O-(2' E,4' Z)-tetradecadienoate (3), and 5,20-O-isopropylidenylingenol 3-O-(2' E,4' Z)-tetradecadienoate (4) were isolated. Their structures(More)
The alpha2 adrenergic receptor (α(2)-AR) antagonist yohimbine is a widely used tool for the study of anxiogenesis and stress-induced drug-seeking behavior. We previously demonstrated that yohimbine paradoxically depresses excitatory transmission in the bed nucleus of the stria terminalis (BNST), a region critical to the integration of stress and reward(More)
The pyrimidopurinone adduct M1G [3-(2'-deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1,2-a]-purin-10(3H)-one], formed in DNA upon exposure to malondialdehyde or base propenals, was incorporated into 5'-d(ATCGCMCGGCATG)-3'-5'-d(CATGCCGCGAT)-3', where M = M1G. This duplex contained a two-nucleotide bulge in the modified strand, and was named the M1G-2BD(More)
Previous studies from our laboratory have revealed that esterification/amidation of the carboxylic acid moiety in the nonsteroidal anti-inflammatory drug, indomethacin, generates potent and selective COX-2 inhibitors. In the present study, a series of reverse ester/amide derivatives were synthesized and evaluated as selective COX-2 inhibitors. Most of the(More)
The OPdG adduct N (2)-(3-oxo-1-propenyl)dG, formed in DNA exposed to malondialdehyde, was introduced into 5'-d(ATCGC XCGGCATG)-3'.5'-d(CATGCCGCGAT)-3' at pH 7 (X = OPdG). The OPdG adduct is the base-catalyzed rearrangement product of the M 1dG adduct, 3-(beta- d-ribofuranosyl)pyrimido[1,2- a]purin-10(3 H)-one. This duplex, named the OPdG-2BD(More)
Malondialdehyde (MDA) is a toxic and mutagenic metabolite produced by lipid peroxidation, and prostaglandin biosynthesis. MDA induces frameshift mutations in tester strains of Salmonella typhimurium. It reacts with DNA, and at physiological pH the major adduct is a pyrimidopurinone formed by reaction with guanine: M1G(More)
A high-throughput cell-based screen identified a series of 6-substituted-4-anilinoquinazolines as non-competitive antagonists of metabotropic glutamate receptor 5 (mGlu(5)). This Letter describes the SAR of this series and the profile of selected compounds in selectivity and radioligand binding assays.
This Letter describes the continued optimization of the MLPCN probe molecule ML071. After introducing numerous cyclic constraints and novel substitutions throughout the parent structure, we produced a number of more highly potent agonists of the M(1) mACh receptor. While many novel agonists demonstrated a promising ability to increase soluble APPα release,(More)