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Full-Text Articles in Chemistry
A Set Of Phosphatase-Inert “Molecular Rulers” To Probe For Bivalent Mannose 6-Phosphate Ligand-Receptor Interactions, Xiang Fei, Christopher M. Connelly, Richard G. Macdonald, David B. Berkowitz
A Set Of Phosphatase-Inert “Molecular Rulers” To Probe For Bivalent Mannose 6-Phosphate Ligand-Receptor Interactions, Xiang Fei, Christopher M. Connelly, Richard G. Macdonald, David B. Berkowitz
David Berkowitz Publications
A set of bivalent mannose 6-phosphonate “molecular rulers” has been synthesized to examine ligand binding to the M6P/IGF2R. The set is estimated to span a P-P distance range of 16-26 Å (MMFF energy minimization on the hydrated phosphonates). Key synthetic transformations include sugar triflate displacement for phosphonate installation and Grubbs I cross-metathesis to achieve bivalency. Relative binding affinities were tested by radioligand displacement assays versus PMP-BSA (pentamannose phosphate-bovine serum albumin). These compounds exhibit slightly higher binding affinities for the receptor (IC50’s = 3.7-5 &#;M) than the parent, monomeric mannose 6-phosphonate ligand and M6P itself (IC50 = 11.5 …
Topoisomerase Ii-Drug Interaction Domains: Identification Of Substituents On Etoposide That Interact With The Enzyme, Amy M. Wilstermann, Ryan P. Bender, Murrell Godfrey, Sungjo Choi, Clemens Anklin, David B. Berkowitz, Neil Osheroff, David E. Graves
Topoisomerase Ii-Drug Interaction Domains: Identification Of Substituents On Etoposide That Interact With The Enzyme, Amy M. Wilstermann, Ryan P. Bender, Murrell Godfrey, Sungjo Choi, Clemens Anklin, David B. Berkowitz, Neil Osheroff, David E. Graves
David Berkowitz Publications
Etoposide is one of the most successful chemotherapeutic agents used for the treatment of human cancers. The drug kills cells by inhibiting the ability of topoisomerase II to ligate nucleic acids that it cleaves during the double-stranded DNA passage reaction. Etoposide is composed of a polycyclic ring system (rings A–D), a glycosidic moiety at the C4 position, and a pendant ring (E–ring) at the C1 position. Although drug-enzyme contacts, as opposed to drug-DNA interactions, mediate the entry of etoposide into the topoisomerase II-drug-DNA complex, the substituents on etoposide that interact with the enzyme have not been identified. Therefore, saturation transfer …
Examination Of The New Α-(2′Z-Fluoro)Vinyl Trigger With Lysine Decarboxylase: The Absolute Stereochemistry Dictates The Reaction Course, Kannan R. Karukurichi, Roberto De La Salud-Bea, Wan Jin Jahng, David B. Berkowitz
Examination Of The New Α-(2′Z-Fluoro)Vinyl Trigger With Lysine Decarboxylase: The Absolute Stereochemistry Dictates The Reaction Course, Kannan R. Karukurichi, Roberto De La Salud-Bea, Wan Jin Jahng, David B. Berkowitz
David Berkowitz Publications
The first examination of a terminal α-fluorovinyl trigger in an amino acid decarboxylase active site is reported. To investigate the enantiospecifity of inactivation with this new AADC trigger, an enantioselective synthesis of L-α-(2′Z-fluoro)vinyllysine and its D-antipode has been developed. Control of stereochemistry is achieved through introduction of the amino acid side chain via alkylation of a chiral vinylglycine-derived dienolate. Facial selectivity is conferred by a trans-2′(β- naphthyl)-2′-propylcyclohexyl ester auxiliary, available in both antipodal forms (Comins protocol). The alkylation employs a new electrophile, N-p-methoxybenzyl-N-(2′- trimethylsilylethanesulfonyl)-4-iodobutylamine, for convergent installation of the lysine side chain. Vinyl to 2′-fluorovinyl interconversion then provides L- …