142072-07-9Relevant articles and documents
Evidence That Nucleophile Deprotonation Exceeds Bond Formation in the HDV Ribozyme Transition State
Lu, Jun,Koo, Selene C.,Weissman, Benjamin P.,Harris, Michael E.,Li, Nan-Sheng,Piccirilli, Joseph A.
, p. 3465 - 3472 (2018)
Steric constraints imposed by the active sites of protein and RNA enzymes pose major challenges to the investigation of structure-function relationships within these systems. As a strategy to circumvent such constraints in the HDV ribozyme, we have synthesized phosphoramidites from propanediol derivatives and incorporated them at the 5′-termini of RNA and DNA oligonucleotides to generate a series of novel substrates with nucleophiles perturbed electronically through geminal fluorination. In nonenzymatic, hydroxide-catalyzed intramolecular transphosphorylation of the DNA substrates, pH-rate profiles revealed that fluorine substitution reduces the maximal rate and the kinetic pKa, consistent with the expected electron-withdrawing effect. In HDV ribozyme reactions, we observed that the RNA substrates undergo transphosphorylation relatively efficiently, suggesting that the conformational constraints imposed by a ribofuranose ring are not strictly required for ribozyme catalysis. In contrast to the nonenzymatic reactions, however, substrate fluorination modestly increases the ribozyme reaction rate, consistent with a mechanism in which (1) the 2′-hydroxyl nucleophile exists predominantly in its neutral, protonated form in the ground state and (2) the 2′-hydroxyl bears some negative charge in the rate-determining step, consistent with a transition state in which the extent of 2′-OH deprotonation exceeds the extent of P-O bond formation.
AZA-BENZOFURANYL COMPOUNDS AND METHODS OF USE
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Page/Page column 117, (2008/06/13)
The invention relates to azabenzofuranyl compounds of Formula (I) with anti-cancer and/or anti-inflammatory activity and more specifically to azabenzofuranyl compounds which inhibit MEK kinase activity. The invention provides compositions and methods useful for inhibiting abnormal cell growth or treating a hyperproliferative disorder, or treating an inflammatory disease in a mammal. The invention also relates to methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.
A Novel Deacylation Method using Grignard Reagent without affecting the Neighbouring Base-sensitive Functional Groups
Watanabe, Yutaka,Fujimoto, Takahiro,Ozaki, Shoichiro
, p. 681 - 683 (2007/10/02)
Methyl and ethyl Grignard reagents are shown to cleave ester functions such as benzoate and acetate without affecting the neighbouring base-sensitive functional groups.
