A5000951184- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- CRISPR and Genetic Engineering
- Polyamine Metabolism and Applications
- Sirtuins and Resveratrol in Medicine
- Carbohydrate Chemistry and Synthesis
- Biochemical and Molecular Research
- Nanomaterials for catalytic reactions
- Magnetic confinement fusion research
- Epigenetics and DNA Methylation
- Cancer-related gene regulation
- Particle Accelerators and Free-Electron Lasers
- Innovative Microfluidic and Catalytic Techniques Innovation
- Crystallography and molecular interactions
- Physics of Superconductivity and Magnetism
- Autophagy in Disease and Therapy
Harvard University
2019-2020
Brookhaven National Laboratory
2015
Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme that methylates nicotinamide (NAM) using cofactor S-adenosylmethionine (SAM). NNMT overexpression has been linked to diabetes, obesity, and various cancers. In this work, structure-based rational design led the development of potent selective alkynyl bisubstrate inhibitors NNMT. The reported nicotinamide–SAM conjugate (named NS1) features an alkyne as key element closely mimics linear, 180° transition state geometry found in...
The natural nucleoside (+)-sinefungin, structurally similar to cofactor S-adenosyl-l-methionine, inhibits various SAM-dependent methyltransferases (MTs). Access sinefungin analogues could serve as the basis for rational design of small molecule methyltransferase inhibitors. We developed a route unnatural C9′ epimer that employed diastereoselective Overman rearrangement install key C6′ amino stereocenter. ability late-stage modification is highlighted, opening an avenue discovery new MT
<div> <p>In this work, structure-based rational design led to the development of potent and selective alkynyl bisubstrate inhibitors NNMT. The reported nicotinamide-SAM conjugate (named <b>NS1</b>) features an alkyne as a key element that closely mimics linear, 180° transition state geometry found in NNMT-catalyzed SAM → NAM (nicotinamide) methyl transfer reaction. NS1 was synthesized single enantiomer diastereomer 14 steps be high-affinity, subnanomolar NNMT...
The natural nucleoside (+)-sinefungin, structurally similar to cofactor S-adenosyl-L-methionine (SAM), inhibits various SAM-dependent methyltransferases (MTs). Access sinefungin analogues could serve as the basis for rational design of small-molecule methyltransferase inhibitors. We developed a route unnatural C9’ epimer that employed diastereoselective Overman rearrangement install key C6’ amino stereocenter. ability late stage modification is highlighted, opening an avenue discovery new MTs
The natural nucleoside (+)-sinefungin, structurally similar to cofactor <i>S</i>-adenosyl-<i>L</i>-methionine (SAM), inhibits various SAM-dependent methyltransferases (MTs). Access sinefungin analogues could serve as the basis for rational design of small-molecule methyltransferase inhibitors. We developed a route unnatural C9’ epimer that employed diastereoselective Overman rearrangement install key C6’ amino stereocenter. ability late stage modification is...
In this work, structure-based rational design led to the development of potent and selective alkynyl bisubstrate inhibitors NNMT. The reported nicotinamide-SAM conjugate (named NS1 ) features an alkyne as a key element that closely mimics linear, 180° transition state geometry found in NNMT-catalyzed SAM → NAM (nicotinamide) methyl transfer reaction. was synthesized single enantiomer diastereomer 14 steps be high-affinity, subnanomolar NNMT inhibitor. An X-ray co-crystal structure...