Computer Review of ChemDraw Ultra 12.0

Cousins, Kimberley

doi:10.1021/ja204075s

Cited by 211 publications

(97 citation statements)

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“…The molecular docking study was performed on an Asus personal computer with Intel(R) Core(TM) 2 Quad 2.4 GHz processor, running Windows 7 using ChemBioOffice 2008 [28] and Discovery Studio 3.0 (DS 3.0). The crystal structure was downloaded from the Protein Data Bank (http://www.rcsb.org/pdb/index.html; PDB code: 4EKZ).…”

Section: Methodsmentioning

confidence: 99%

HPW-RX40 prevents human platelet activation by attenuating cell surface protein disulfide isomerases

et al. 2017

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Protein disulfide isomerase (PDI) present at platelet surfaces has been considered to play an important role in the conformational change and activation of the integrin glycoprotein IIb/IIIa (GPIIb/IIIa) and thus enhances platelet aggregation. Growing evidences indicated that platelet surface PDI may serve as a potential target for developing of a new class of antithrombotic agents. In the present study, we investigated the effects of HPW-RX40, a chemical derivative of β-nitrostyrene, on platelet activation and PDI activity. HPW-RX40 inhibited platelet aggregation, GPIIb/IIIa activation, and P-selectin expression in human platelets. Moreover, HPW-RX40 reduced thrombus formation in human whole blood under flow conditions, and protects mice from FeCl3-induced carotid artery occlusion. HPW-RX40 inhibited the activity of recombinant PDI family proteins (PDI, ERp57, and ERp5) as well as suppressed cell surface PDI activity of platelets in a reversible manner. Exogenous addition of PDI attenuated the inhibitory effect of HPW-RX40 on GPIIb/IIIa activation. Structure-based molecular docking simulations indicated that HPW-RX40 binds to the active site of PDI by forming hydrogen bonds. In addition, HPW-RX40 neither affected the cell viability nor induced endoplasmic reticulum stress in human cancer A549 and MDA-MB-231 cells. Taken together, our results suggest that HPW-RX40 is a reversible and non-cytotoxic PDI inhibitor with antiplatelet effects, and it may have a potential for development of novel antithrombotic agents.

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Section: Methodsmentioning

confidence: 99%

HPW-RX40 prevents human platelet activation by attenuating cell surface protein disulfide isomerases

et al. 2017

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“…The thiostrepton analogs, Ala4Cys F1 and F2, were manually built in ChemDraw 3D using the crystal structure of thiostrepton A complexed to the ribosome (PDB entry: 3CF5) as the template. (57) The analog structures were energy-minimized using the MM2 force field in ChemDraw 3D, where H43/44 and L11 were immobilized during minimization. (58) The interactions between the energy minimized structures of the thiostrepton Ala4Cys analogs and the ribosome were visualized using PyMOL.…”

Section: Methodsmentioning

confidence: 99%

Saturation Mutagenesis of TsrA Ala4 Unveils a Highly Mutable Residue of Thiostrepton A

Zhang

Kelly

2015

ACS Chem. Biol.

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Thiopeptides are posttranslationally processed macrocyclic peptide metabolites, characterized by extensive backbone and side chain modifications that include a six-membered nitrogeneous ring, thiazol(in)e/oxazol(in)e rings, and dehydrated amino acid residues. Thiostrepton A, one of the more structurally complex and well-studied thiopeptides, contains a second macrocycle bearing a quinaldic acid moiety. Antibacterial, antimalarial, and anticancer properties have been described for thiostrepton A and other thiopeptides, although the molecular details for binding the cellular target in each case are not fully elaborated. We previously demonstrated that a mutation of the TsrA core peptide, Ala4Gly, supported the successful production of the corresponding thiostrepton variant. To more thoroughly probe the thiostrepton biosynthetic machinery’s tolerance toward structural variation at the fourth position of the TsrA core peptide, we report here the saturation mutagenesis of this residue using a fosmid-dependent biosynthetic engineering method and the isolation of 16 thiostrepton analogs. Several types of side chain substitutions at the fourth position of TsrA, including those that introduce polar or branched, hydrophobic residues, are accepted, albeit with varied preferences. In contrast, proline and amino acid residues inherently charged at physiological pH are not well-tolerated at the queried site by the thiostrepton biosynthetic system. These newly generated thiostrepton analogs were assessed for their antibacterial activities and abilities to inhibit the proteolytic functions of the eukaryotic 20S proteasome. We demonstrate that the identity of the fourth amino acid residue in the thiostrepton scaffold is not critical for either ribosome or proteasome inhibition.

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“…The structures of the 211 partial agonists were built with ChemDraw Ultra v11.0 (CambridgeSoft Corporation, Cambridge, MA, USA; http://www.cambridgesoft.com/) [45] and were cleaned using LigPrep v2.3 (Schrödinger LLC., Portland, USA; http://www.schrodinger.com). We calculated an EF and values for sensitivity ( Se ) and specificity ( Sp ) for the global VS workflow and each step [46].…”

Section: Methodsmentioning

confidence: 99%

Identification of PPARgamma Partial Agonists of Natural Origin (II): In Silico Prediction in Natural Extracts with Known Antidiabetic Activity

et al. 2013

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BackgroundNatural extracts have played an important role in the prevention and treatment of diseases and are important sources for drug discovery. However, to be effectively used in these processes, natural extracts must be characterized through the identification of their active compounds and their modes of action.Methodology/Principal FindingsFrom an initial set of 29,779 natural products that are annotated with their natural source and using a previously developed virtual screening procedure (carefully validated experimentally), we have predicted as potential peroxisome proliferators-activated receptor gamma (PPARγ) partial agonists 12 molecules from 11 extracts known to have antidiabetic activity. Six of these molecules are similar to molecules with described antidiabetic activity but whose mechanism of action is unknown. Therefore, it is plausible that these 12 molecules could be the bioactive molecules responsible, at least in part, for the antidiabetic activity of the extracts containing them. In addition, we have also identified as potential PPARγ partial agonists 10 molecules from 16 plants with undescribed antidiabetic activity but that are related (i.e., they are from the same genus) to plants with known antidiabetic properties. None of the 22 molecules that we predict as PPARγ partial agonists show chemical similarity with a group of 211 known PPARγ partial agonists obtained from the literature.Conclusions/SignificanceOur results provide a new hypothesis about the active molecules of natural extracts with antidiabetic properties and their mode of action. We also suggest plants with undescribed antidiabetic activity that may contain PPARγ partial agonists. These plants represent a new source of potential antidiabetic extracts. Consequently, our work opens the door to the discovery of new antidiabetic extracts and molecules that can be of use, for instance, in the design of new antidiabetic drugs or functional foods focused towards the prevention/treatment of type 2 Diabetes Mellitus.

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Computer Review of ChemDraw Ultra 12.0

Cited by 211 publications

References 1 publication

HPW-RX40 prevents human platelet activation by attenuating cell surface protein disulfide isomerases

HPW-RX40 prevents human platelet activation by attenuating cell surface protein disulfide isomerases

Saturation Mutagenesis of TsrA Ala4 Unveils a Highly Mutable Residue of Thiostrepton A

Identification of PPARgamma Partial Agonists of Natural Origin (II): In Silico Prediction in Natural Extracts with Known Antidiabetic Activity

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