2024
Synthesis of (2R,4S)‑4-Amino-5-hydroxybicyclo[3.1.1]heptane-2-carboxylic Acid via an Asymmetric Intramolecular Mannich Reaction
Dukes A, Weerawarna P, Devitt A, Silverman R. Synthesis of (2R,4S)‑4-Amino-5-hydroxybicyclo[3.1.1]heptane-2-carboxylic Acid via an Asymmetric Intramolecular Mannich Reaction. The Journal Of Organic Chemistry 2024, 89: 9110-9117. PMID: 38857432, PMCID: PMC11418922, DOI: 10.1021/acs.joc.4c00781.Peer-Reviewed Original ResearchDesign, Synthesis, and Mechanistic Studies of (R)‑3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase
Devitt A, Vargas A, Zhu W, Soye B, Butun F, Alt T, Kaley N, Ferreira G, Moran G, Kelleher N, Liu D, Silverman R. Design, Synthesis, and Mechanistic Studies of (R)‑3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase. ACS Chemical Biology 2024, 19: 1066-1081. PMID: 38630468, PMCID: PMC11274680, DOI: 10.1021/acschembio.4c00022.Peer-Reviewed Original ResearchConceptsActive siteX-ray crystallographyIntact protein mass spectrometryHuman ornithine aminotransferaseNucleophilic additionRing scaffoldMass spectrometryIntermediate speciesProtein mass spectrometryIncreased selectivityTransient state kinetic studiesX-rayMechanistic studiesAdductsSolvent accessibilityKinetic studiesHepatocellular carcinomaProgression of hepatocellular carcinomaMechanism of inactivationStructural evidencePrevalence of hepatocellular carcinomaTreatment of hepatocellular carcinomaCyclohexeneCyclopenteneCrystallography
2021
Pregabalin Treatment does not Affect Amyloid Pathology in 5XFAD Mice
Sadleir K, Popovoic J, Zhu W, Reidel C, Do H, Silverman R, Vassar R. Pregabalin Treatment does not Affect Amyloid Pathology in 5XFAD Mice. Current Alzheimer Research 2021, 18: 283-297. PMID: 34259145, PMCID: PMC9527523, DOI: 10.2174/1567205018666210713125333.Peer-Reviewed Original ResearchConceptsVoltagegated calcium channelsPlacebo-treated miceNeuropathic painPregabalin treatmentStatistically significant positive correlationCalcium channelsCalcium influxAb levelsDecreased markersPregabalinSignificant positive correlationCerebral concentrationsEffective treatmentAmyloid depositsCausative roleDystrophyCalcium dysregulationMiceNeuritic dystrophyProgression of amyloid pathologyPathologyImmunofluorescence imagingNeuronal processesPlaqueTreatment
2008
From Basic Science to Blockbuster Drug: The Discovery of Lyrica
Silverman R. From Basic Science to Blockbuster Drug: The Discovery of Lyrica. Angewandte Chemie International Edition 2008, 47: 3500-3504. PMID: 18307181, DOI: 10.1002/anie.200704280.Peer-Reviewed Original Research