Medicinal Chemistry
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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 ... -
Evaluation of Biased and Balanced Salvinorin A Analogs in Preclinical Models of Pain
(Frontiers Media, 2020-07-21)In the search for safer, non-addictive analgesics, kappa opioid receptor (KOPr) agonists are a potential target, as unlike mu-opioid analgesics, they do not have abuse potential. Salvinorin A (SalA) is a potent and selective ... -
Synthetic lethality by targeting the RUVBL1/2-TTT complex in mTORC1-hyperactive cancer cells
(American Association for the Advancement of Science, 2020-07-31)Despite considerable efforts, mTOR inhibitors have produced limited success in the clinic. To define the vulnerabilities of mTORC1-addicted cancer cells and to find previously unknown therapeutic targets, we investigated ... -
Phenylalanine Stereoisomers of CJ-15,208 and [d-Trp]CJ-15,208 Exhibit Distinctly Different Opioid Activity Profiles
(MDPI, 2020-09-02)The macrocyclic tetrapeptide cyclo[Phe-d-Pro-Phe-Trp] (CJ-15,208) and its stereoisomer cyclo[Phe-d-Pro-Phe-d-Trp] exhibit different opioid activity profiles in vivo. The present study evaluated the influence of the Phe ... -
Design of Substrate Transmembrane Mimetics as Structural Probes for γ-Secretase
(American Chemical Society, 2020-01-30)γ-Secretase is a membrane-embedded aspartyl protease complex central in biology and medicine. How this enzyme recognizes transmembrane substrates and catalyzes hydrolysis in the lipid bilayer is unclear. Inhibitors that ... -
Reactive Metabolite Target Protein Database (TPDB)
(2020-08-03)The biotransformation of drugs and xenobiotic chemicals in living cells sometimes generates chemically reactive metabolites (CRMs) that diffuse through the cell and react covalently with cellular constituents, especially ... -
The Meta-Position of Phe4 in Leu-Enkephalin Regulates Potency, Selectivity, Functional Activity, and Signaling Bias at the Delta and Mu Opioid Receptors
(MDPI, 2019-12-12)As tool compounds to study cardiac ischemia, the endogenous δ-opioid receptors (δOR) agonist Leu5-enkephalin and the more metabolically stable synthetic peptide (d-Ala2, d-Leu5)-enkephalin are frequently employed. However, ... -
Bioactivity Profiling of Plant Biodiversity of Panama by High Throughput Screening
(SAGE Publications, 2019-01-01)We report relative bioactivities of extracts prepared from a large collection of plants from three national parks in Panama. Over 181 plants were collected, taxonomically identified and their detannified dichloromethane ... -
Dysfunctional γ-Secretase in Familial Alzheimer’s Disease
(Springer Verlag, 2019-01-01)Genetics strongly implicate the amyloid β-peptide (Aβ) in the pathogenesis of Alzheimer’s disease. Dominant missense mutation in the presenilins and the amyloid precursor protein (APP) cause early-onset familial Alzheimer’s ... -
Membrane protein takes the brakes off
(American Association for the Advancement of Science, 2019-02-01) -
Structure and Function of the γ-Secretase Complex
(American Chemical Society, 2019-06-14)γ-Secretase is a membrane-embedded protease complex, with presenilin as the catalytic component containing two transmembrane aspartates in the active site. With more than 90 known substrates, the γ-secretase complex is ... -
The β20–β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions
(Nature Research, 2017-10-19)The entry of HIV-1 into target cells is mediated by the viral envelope glycoproteins (Env). Binding to the CD4 receptor triggers a cascade of conformational changes in distant domains that move Env from a functionally ...
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