Medicinal Chemistry
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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 ... -
Combining flavin photocatalysis with parallel synthesis: a general platform to optimize peptides with non-proteinogenic amino acids
(Royal Society of Chemistry, 2021-06-30)Most peptide drugs contain non-proteinogenic amino acids (NPAAs), born out through extensive structure–activity relationship (SAR) studies using solid-phase peptide synthesis (SPPS). Synthetically laborious and expensive ... -
Recognition of single-stranded nucleic acids by small-molecule splicing modulators
(Oxford University Press, 2021-07-20)Risdiplam is the first approved small-molecule splicing modulator for the treatment of spinal muscular atrophy (SMA). Previous studies demonstrated that risdiplam analogues have two separate binding sites in exon 7 of the ... -
Quantification of kappa opioid receptor ligand potency, efficacy and desensitization using a real-time membrane potential assay
(Elsevier, 2021-11)We explored the utility of the real-time FLIPR Membrane Potential (FMP) assay as a method to assess kappa opioid receptor (KOR)-induced hyperpolarization. The FMP Blue dye was used to measure fluorescent signals reflecting ... -
Lithium perchlorate-, acetic anhydride-, and triphenylphosphine-assisted multicomponent syntheses of 4-unsubstituted 2,5-dioxooctahydroquinoline-3-carboxylates and 3-carbonitriles
(Elsevier, 2013-09-05)Lithium perchlorate and acetic anhydride were the key additives for the multi-component reaction between 3-aminocyclohex-2-enones, formaldehyde, and malonates yielding adducts that were annulated under acidic conditions ... -
A cellular complex of BACE1 and γ-secretase sequentially generates Aβ from its full-length precursor
(Rockefeller University Press, 2019-01-09)Intramembrane proteolysis of transmembrane substrates by the presenilin–γ-secretase complex is preceded and regulated by shedding of the substrate’s ectodomain by α- or β-secretase. We asked whether β- and γ-secretases ... -
Mimicry in viceroy butterflies is dependent on abundance of the model queen butterfly
(Nature Research, 2019-02-18)Mimics should not exist without their models, yet often they do. In the system involving queen and viceroy butterflies, the viceroy is both mimic and co-model depending on the local abundance of the model, the queen. Here, ... -
Antibody–Drug Conjugate that Exhibits Synergistic Cytotoxicity with an Endosome–Disruptive Peptide
(American Chemical Society, 2019-07-31)Antibody–drug conjugates are an important class of cancer therapeutics. These agents generally bind a specific cell surface receptor, undergo receptor-mediated endocytosis, and enter the endosomal–lysosomal system, where ... -
Structure of the Diphtheria Toxin at Acidic pH: Implications for the Conformational Switching of the Translocation Domain
(MDPI, 2020-11-07)Diphtheria toxin, an exotoxin secreted by Corynebacterium that causes disease in humans by inhibiting protein synthesis, enters the cell via receptor-mediated endocytosis. The subsequent endosomal acidification triggers a ... -
Relative Selectivity of Plant Cardenolides for Na+/K+-ATPases From the Monarch Butterfly and Non-resistant Insects
(Frontiers Media, 2018-09-28)A major prediction of coevolutionary theory is that plants may target particular herbivores with secondary compounds that are selectively defensive. The highly specialized monarch butterfly (Danaus plexippus) copes well ... -
Improved Schmidt Conversion of Aldehydes to Nitriles Using Azidotrimethylsilane in 1,1,1,3,3,3-Hexafluoro-2-propanol
(MDPI, 2015-12-29)The Schmidt reaction of aromatic aldehydes using a substoichiometric amount (40 mol %) of triflic acid is described. Low catalyst loading was enabled by a strong hydrogen-bond-donating solvent hexafluoro-2-propanol (HFIP). ... -
Pharmacokinetic evaluation of the PNC disassembler metarrestin in wild-type and Pdx1-Cre;LSL-KrasG12D/+;Tp53R172H/+ (KPC) mice, a genetically engineered model of pancreatic cancer
(Springer, 2018-10-10)Purpose Metarrestin is a first-in-class small molecule clinical candidate capable of disrupting the perinucleolar compartment, a subnuclear structure unique to metastatic cancer cells. This study aims to define the ... -
Mimicry in viceroy butterflies is dependent on abundance of the model queen butterfly
(Nature Research, 2019-02-18)Mimics should not exist without their models, yet often they do. In the system involving queen and viceroy butterflies, the viceroy is both mimic and co-model depending on the local abundance of the model, the queen. Here, ... -
The Intriguing Effects of Substituents in the N-Phenethyl Moiety of Norhydromorphone: A Bifunctional Opioid from a Set of “Tail Wags Dog” Experiments
(MDPI, 2020-06-06)(−)-N-Phenethyl analogs of optically pure N-norhydromorphone were synthesized and pharmacologically evaluated in several in vitro assays (opioid receptor binding, stimulation of [35S]GTPγS binding, forskolin-induced cAMP ...
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