Medicinal Chemistry
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Swe1Wee1-dependent tyrosine phosphorylation of Hsp90 regulates distinct facets of chaperone function
(Elsevier, 2010-02-12)Swe1 (Saccharomyces WEE1), the only “true” tyrosine kinase in budding yeast, is an Hsp90 client protein. Here we show that Swe1Wee1 phosphorylates a conserved tyrosine residue (Y24 in yeast Hsp90 and Y38 in human Hsp90α) ... -
Triazole Containing Novobiocin and Biphenyl Amides as Hsp90 C-Terminal Inhibitors
(Royal Society of Chemistry, 2017-09-01)Hsp90 C-terminal inhibitors are advantageous for the development of new cancer chemotherapeutics due to their ability to segregate client protein degradation from induction of the prosurvival heat shock response, which is ... -
Potential Drug Abuse Therapeutics Derived from the Hallucinogenic Natural Product Salvinorin A
(Royal Society of Chemistry, 2011-12)Previous structure-activity relationship studies of salvinorin A have shown that modification of the acetate functionality off the C-2 position to a methoxy methyl or methoxy ethyl ether moiety leads to increased potency ... -
Interaction of 3â-amino-5-cholestene with phospholipids in binary and ternary bilayer membranes
(American Chemical Society, 2012-01-10)3β-Amino-5-cholestene (aminocholesterol) is a synthetic sterol whose properties in bilayer membranes have been examined. In fluid palmitoyl sphingomyelin (PSM) bilayers, aminocholesterol and cholesterol were equally effective ... -
Protection of Trabecular Bone in Ovariectomized Rats by Turmeric (Curcuma longa L.) is Dependent on Extract Composition
(American Chemical Society, 2010-09-08)Extracts prepared from turmeric (Curcuma longa L., [Zingiberaceae]) containing bioactive phenolic curcuminoids were evaluated for bone-protective effects in a hypogonadal rat model of postmenopausal osteoporosis. Three-month ... -
Anti-Arthritic Effects and Toxicity of the Essential Oils of Turmeric (Curcuma longa L.)
(American Chemical Society, 2010-01-27)Abstract Turmeric (Curcuma longa L., Zingiberaceae) rhizomes contain two classes of secondary metabolites, curcuminoids and the less well-studied essential oils. Having previously identified potent anti-arthritic effects ... -
Oxidative cytotoxic agent withaferin A resensitizes temozolomide-resistant glioblastomas via MGMT depletion and induces apoptosis through Akt/mTOR pathway inhibitory modulation
(Springer Verlag, 2014-08)Temozolomide (TMZ) has remained the chemotherapy of choice in patients with glioblastoma multiforme (GBM) primarily due to the lack of more effective drugs. Tumors, however, quickly develop resistance to this line of ... -
Cytotoxicity of withaferin A in glioblastomas involves induction of an oxidative stress-mediated heat shock response while altering Akt/mTOR and MAPK signaling pathways
(Springer Verlag, 2013-06)Withaferin A (WA), a steroidal lactone derived from the plant Vassobia breviflora, has been reported to have anti-proliferative, pro-apoptotic, and anti-angiogenic properties against cancer growth. In this study, we ... -
Structural comparison of cytochromes P450 2A6, 2A13, and 2E1 with pilocarpine†
(Wiley, 2012-05)Human xenobiotic-metabolizing cytochrome P450 (P450) enzymes can each bind and monooxygenate a diverse set of substrates, including drugs, often producing a variety of metabolites. Additionally a single ligand can interact ... -
Design, Synthesis and Biological Evaluation of Biphenylamide Derivatives as Hsp90 C-terminal Inhibitors
(Elsevier, 2015-01-07)Modulation of Hsp90 C-terminal function represents a promising therapeutic approach for the treatment of cancer and neurodegenerative diseases. Current drug discovery efforts toward Hsp90 C-terminal inhibition focus on ... -
Collision Induced Dissociation Products of Disulfide-bonded Peptides: Ions Result from the Cleavage of More than One Bond
(American Chemical Society, 2011-03)Disulfide bonds are a posttranslational modification (PTM) that can be scrambled or shuffled to non-native bonds during recombinant expression, sample handling, or sample purification. Currently, mapping of disulfide bonds ... -
Analysis of Overlapped and Noisy Hydrogen/Deuterium Exchange Mass Spectra
(American Chemical Society, 2013-12)Noisy and overlapped mass spectrometry data hinders the sequence coverage that can be obtained from Hydrogen Deuterium exchange analysis, and places a limit on the complexity of the samples that can be studied by this ... -
Structural Characterization of N-Protonated Amides. Regioselective N-Protonated Amides. Regioselective N-Activation of Medium-Bridged Twisted Lactams
(American Chemical Society, 2010-07-07)The straightforward protonation of lactams by treatment with acid and the full structural characterization of three resulting N-protonated lactams are disclosed. This work provides experimental evidence that N-protonation ... -
Novobiocin Analogs That Inhibit the MAPK Pathway
(American Chemical Society, 2016-02-11)Heat shock protein 90 (Hsp90) inhibition by modulation of the N-or C-terminal binding site has become an attractive strategy for the development of anti-cancer chemotherapeutics. The first Hsp90 C-terminus inhibitor, ... -
Development of a Grp94 inhibitor
(American Chemical Society, 2012-06-13)Heat shock protein 90 (Hsp90) represents a promising therapeutic target for the treatment of cancer and other diseases. Unfortunately, results from clinical trials have been disappointing as off-target effects and toxicities ... -
Filing and Mining the Reactive Metabolite Target Protein Database
(Elsevier, 2009-04-15)The post-translational modification of proteins is a well-known endogenous mechanism for regulating protein function and activity. Cellular proteins are also susceptible to post-translational modification by xenobiotic ... -
Novologues Containing a Benzamide Side Chain Manifest Anti-proliferative Activity Against Two Breast Cancer Cell Lines
(Elsevier, 2014-08-01)The heat shock protein 90 (Hsp90) folding machinery is essential for the maturation of nascent polypeptides into their biologically active three-dimensional-structures and for the rematuration/clearance of misfolded proteins ... -
Synthesis of carbon-14, carbon-13 and deuterium labeled forms of thioacetamide and thioacetamide S-oxide
(Wiley, 2011-11)Thioacetamide (TA) is a model hepatotoxin that undergoes metabolic activation via two successive S-oxidations. The ultimate toxic metabolite thioacetamide S,S-dioxide, or its tautomer acetimidoyl sulfinic acid CH3C(NH)SO2H, ... -
Exploiting conformational dynamics in drug discovery: design of C-terminal inhibitors of Hsp90 with improved activities
(American Chemical Society, 2014-01-27)The interaction that occurs between molecules is a dynamic process that impacts both structural and conformational properties of the ligand and the ligand binding site. Herein, we investigate the dynamic cross-talk between ... -
Discovery of a Novel Selective Kappa-Opioid Receptor Agonist Using Crystal Structure-Based Virtual Screening
(American Chemical Society, 2013-03-25)Kappa-opioid (KOP) receptor agonists exhibit analgesic effects without activating reward pathways. In the search for non-addictive opioid therapeutics and novel chemical tools to study physiological functions regulated by ...
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