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Medicinal Chemistry Scholarly Works: Recent submissions
Now showing items 41-60 of 255
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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 ... -
Total Synthesis and Structure–Activity Relationship Studies of the Cytotoxic Anhydrophytosphingosine Jaspine B (Pachastrissamine)
(Thieme Publishing, 2017)By utilizing an l-serine-derived bicyclic lactone as an advanced chiral building block, a short synthetic route to the cytotoxic marine natural product jaspine B has been developed. Targeting structure–activity relationship ... -
Alanine scan of the opioid peptide dynorphin B amide
(American Peptide Society, 2017-05-02)To date structure-activity relationship (SAR) studies of the dynorphins (Dyn), endogenous peptides for kappa opioid receptors (KOR), have focused almost exclusively on Dyn A with minimal studies on Dyn B. While both Dyn A ... -
Novel natural withanolides induce apoptosis and inhibit migration of neuroblastoma cells through down regulation of N-myc and suppression of Akt/mTOR/NF-κB activation
(Impact Journals, 2018-02-07)Despite recent advances in intensive chemotherapy treatments, long-term success is achieved in less than 30% of children with high-risk neuroblastoma (NB). Key regulatory pathways including the PI3K/Akt, mTOR and NF-κB are ... -
Reagent-controlled regiodivergent ring expansions of steroids
(Nature Publishing Group, 2018-03-05)Ring expansion provides a powerful way of introducing a heteroatom substituent into a carbocyclic framework. However, such reactions are often limited by the tendency of a given substrate to afford only one of the two ... -
Molecular Defects in Cardiac Myofilament Ca2+-Regulation Due to Cardiomyopathy-Linked Mutations Can Be Reversed by Small Molecules Binding to Troponin
(Frontiers Media, 2018-03-27)The inherited cardiomyopathies, hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) are relatively common, potentially life-threatening and currently untreatable. Mutations are often in the contractile ... -
Molecular recognition of physiological substrate noradrenaline by the adrenaline synthesising enzyme PNMT and factors influencing its methyltransferase activity
(Portland Press, 2009-09-15)Substrate specificity is critically important for enzyme catalysis. In the adrenaline synthesising enzyme phenylethanolamine N-methyltransferase (PNMT), minor changes in substituents can convert substrates into inhibitors. ... -
Novel C-Terminal Hsp90 Inhibitor for Head and Neck Squamous Cell Cancer (HNSCC) with in vivo Efficacy and Improved Toxicity Profiles Compared with Standard Agents
(Springer Verlag, 2011-08-12)Background - Current therapies for HNSCC, especially platinum agents, are limited by their toxicities and drug resistance. This study evaluates a novel C-terminal Hsp90 inhibitor (CT-Hsp90-I) for efficacy and toxicity in ... -
Stepwise O atom Transfer in Heme-Based Tryptophan Dioxygenase: Role of Substrate Ammonium in Epoxide Ring Opening
(American Chemical Society, 2018-03-28)Heme-based tryptophan dioxygenases are established immunosuppressive metalloproteins with significant biomedical interest. Here, we synthesized two mechanistic probes to specifically test if the α-amino group of the substrate ... -
Structure-Activity Investigation of a G Protein-Biased Agonist Reveals Molecular Determinants for Biased Signaling of the D2 Dopamine Receptor
(Frontiers Media, 2018-02-21)The dopamine D2 receptor (D2R) is known to elicit effects through activating two major signaling pathways mediated by either G proteins (Gi/o) or β-arrestins. However, the specific role of each pathway in physiological or ... -
Structure-guided design of an Hsp90â N-terminal isoform-selective inhibitor
(Nature Publishing Group, 2018-01-30)The 90 kDa heat shock protein (Hsp90) is a molecular chaperone responsible for folding proteins that are directly associated with cancer progression. Consequently, inhibition of the Hsp90 protein folding machinery results ...