Medicinal Chemistry
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Synthesis of Cycloheptatriene-Containing Azetidine Lactones
(American Chemical Society, 2022-05-23)We prepared a collection of complex cycloheptatriene-containing azetidine lactones by applying two key photochemical reactions: “aza-Yang” cyclization and Buchner carbene insertion into aromatic rings. While photolysis of ... -
Highly Regio- and Diastereoselective Tethered Aza-Wacker Cyclizations of Alkenyl Phosphoramidates
(American Chemical Society, 2021-10-19)We present highly diastereoselective tethered aza-Wacker cyclization reactions of alkenyl phosphoramidates. “Arming” the phosphoramidate tether with 5-chloro-8-quinolinol was essential to achieving >20:1 diastereoselectivity ... -
Oxidative Cyclization of Sulfamates onto Pendant Alkenes
(American Chemical Society, 2020-01-13)This communication discloses the first examples of aza-Wacker cyclizations of sulfamate esters. Within the realm of related cyclization reactions, this protocol is differential in that it forms six-membered rings in good ... -
Human cytochrome P450 17A1 structures with metabolites of prostate cancer drug abiraterone reveal substrate-binding plasticity and a second binding site
(Elsevier, 2023-03-09)Abiraterone acetate is a first-line therapy for castration-resistant prostate cancer. This prodrug is deacetylated in vivo to abiraterone, which is a potent and specific inhibitor of cytochrome P450 17A1 (CYP17A1). CYP17A1 ... -
Formulation Studies to Develop Low-cost, Orally-delivered Secretory IgA Monoclonal Antibodies for Passive Immunization Against Enterotoxigenic Escherichia coli (Dataset)
(Elsevier, 2023)Enterotoxigenic Escherichia coli (ETEC) is a common cause for diarrheal infections in children in low- and middle-income countries (LMICs). To date, no ETEC vaccine candidates have been approved. Passive immunization with ... -
Cellular Target Deconvolution of Small Molecules Using a Selection-Based Genetic Screening Platform
(American Chemical Society, 2022-09-22)Small-molecule drug target identification is an essential and often rate-limiting step in phenotypic drug discovery and remains a major challenge. Here, we report a novel platform for target identification of activators ... -
Combination Treatment of Withalongolide a Triacetate with Cisplatin Induces Apoptosis by Targeting Translational Initiation, Migration, and Epithelial to Mesenchymal Transition in Head and Neck Squamous Cell Carcinoma
(MDPI, 2022-12-19)Treatment regimens for head and neck squamous cell carcinoma (HNSCC) typically include cisplatin and radiotherapy and are limited by toxicities. We have identified naturally derived withalongolide A triacetate (WGA-TA) ... -
In-Depth Characterization of Endo-Lysosomal Aβ in Intact Neurons
(MDPI, 2022-08-20)Amyloid-beta (Aβ) peptides are produced within neurons. Some peptides are released into the brain parenchyma, while others are retained inside the neurons. However, the detection of intracellular Aβ remains a challenge ... -
Novel C-terminal heat shock protein 90 inhibitors target breast cancer stem cells and block migration, self-renewal, and epithelial–mesenchymal transition
(Wiley Open Access, 2020-04-07)In patients with triple-negative breast cancer (TNBC), evidence suggests that tumor-initiating cells (TIC) have stem cell-like properties, leading to invasion and metastasis. HSP90 plays a critical role in the conformational ... -
Flavin Metallaphotoredox Catalysis: Synergistic Synthesis in Water
(American Chemical Society, 2022-03-22)Combining a transition metal with a photocatalyst can drive modern synthetic chemistry. For transformations performed in water, this concept has been largely unexplored. We report the successful merger of a biocompatible ... -
Ring Opening of Epoxides by Pendant Silanols
(American Chemical Society, 2022-01-18)We present a new ring-opening reaction of epoxides by pendant silanols, catalyzed by either Ph3C+BF4– or BINOL-phosphoric acid. Silanol epoxides derived from trans-allylic alcohols, cis-allylic alcohols, trans-homoallylic ... -
Mutations in the Amyloid-β Protein Precursor Reduce Mitochondrial Function and Alter Gene Expression Independent of 42-Residue Amyloid-β Peptide
(IOS Press, 2021-09-28)Background:Dominant missense mutations in the amyloid-β protein precursor (AβPP) cause early-onset familial Alzheimer’s disease (FAD) and are associated with changes in the production or properties of the amyloid-β peptide ... -
Inhibition of SARS-CoV-2 by Targeting Conserved Viral RNA Structures and Sequences
(Frontiers Media, 2021-12-23)The ongoing COVID-19/Severe Acute Respiratory Syndrome CoV-2 (SARS-CoV-2) pandemic has become a significant threat to public health and has hugely impacted societies globally. Targeting conserved SARS-CoV-2 RNA structures ... -
The RNA Architecture of the SARS-CoV-2 3′-Untranslated Region
(MDPI, 2020-12-21)Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. The 3′ untranslated region (UTR) of this β-CoV contains essential cis-acting RNA elements for the viral genome ... -
Probing Mechanisms and Therapeutic Potential of γ-Secretase in Alzheimer’s Disease
(MDPI, 2021-01-13)The membrane-embedded γ-secretase complex carries out hydrolysis within the lipid bilayer in proteolyzing nearly 150 different membrane protein substrates. Among these substrates, the amyloid precursor protein (APP) has ... -
Familial Alzheimer’s disease mutations in amyloid protein precursor alter proteolysis by γ-secretase to increase amyloid β-peptides of ≥45 residues
(Elsevier, 2021-01-12)Production of amyloid β-protein (Aβ) is carried out by the membrane-embedded γ-secretase complex. Mutations in the transmembrane domain of amyloid β-protein precursor (APP) associated with early-onset familial Alzheimer's ... -
Hydrophilic loop 1 of Presenilin-1 and the APP GxxxG transmembrane motif regulate γ-secretase function in generating Alzheimer-causing Aβ peptides
(Elsevier, 2021-02-08)γ-Secretase is responsible for the proteolysis of amyloid precursor protein (APP) into amyloid-beta (Aβ) peptides, which are centrally implicated in the pathogenesis of Alzheimer’s disease (AD). The biochemical mechanism ... -
RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays
(MDPI, 2021-04-14)RNA splicing is an essential step in producing mature messenger RNA (mRNA) and other RNA species. Harnessing RNA splicing modifiers as a new pharmacological modality is promising for the treatment of diseases caused by ... -
Salient features of the aza-Wacker cyclization reaction
(Royal Society of Chemistry, 2020-07-21)The intramolecular aza-Wacker reaction has unparalleled potential for the site-selective amination of olefins, but it is perhaps underappreciated relative to other alkene oxidations. The first part of this review makes the ... -
A Formal Rearrangement of Allylic Silanols
(MDPI, 2021-06-23)We show that 1M aqueous HCl/THF or NaBH4/DMF allows for demercurative ring-opening of cyclic organomercurial synthons into secondary silanol products bearing terminal alkenes. We had previously demonstrated that primary ...
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