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  1. AU="Hampton, Joshua Trae"
  2. AU=Thesen Thomas
  3. AU=Oliveira Giuliano da Paz
  4. AU="García, Patricia J"
  5. AU="Hosseinpanah, Farhad"
  6. AU="Mayuni, Grace"
  7. AU="Volkova, Yulia L"
  8. AU="Dauwerse, Sierk"

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  1. Artikel ; Online: RESVERATROL BINDS NUCLEAR RECEPTOR 4A1 (NR4A1) AND ACTS AS AN NR4A1 ANTAGONIST IN LUNG CANCER CELLS

    Zhang, Lei / Martin, Greg / Mohankumar, Kumaravel / Hampton, Joshua Trae / Liu, Wenshe Rayi / Safe, Stephen

    Molecular pharmacology

    2022  

    Abstract: Resveratrol is a polyphenolic phytochemical found in fruits, nuts and vegetables that contributes to the remarkable dietary effects of polyphenolic as inhibitors aging and multiple aging related diseases. In addition, resveratrol has been extensively ... ...

    Abstract Resveratrol is a polyphenolic phytochemical found in fruits, nuts and vegetables that contributes to the remarkable dietary effects of polyphenolic as inhibitors aging and multiple aging related diseases. In addition, resveratrol has been extensively investigated as an inhibitor of inflammatory diseases including cancer, however, the underlying mechanisms of these chemotherapeutic effects of resveratrol are not completely understood. In cancer cells resveratrol inhibits cell growth, survival, migration and invasion, and many of the effects of resveratrol resemble those observed for bis-indole derived (CDIM) compounds that bind the pro-oncogenic nuclear receptor 4A1 (NR4A1, Nur77) and act as receptor antagonists. Using an isothermal titration calorimetry binding assay, we observed that resveratrol bound to the ligand binding domain of NR4A1 with a K
    Sprache Englisch
    Erscheinungsdatum 2022-06-09
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 124034-1
    ISSN 1521-0111 ; 0026-895X
    ISSN (online) 1521-0111
    ISSN 0026-895X
    DOI 10.1124/molpharm.121.000481
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: An amber-encoding helper phage for more efficient phage display of noncanonical amino acids.

    Hampton, Joshua Trae / Cho, Chia-Chuan Dean / Coleman, Demonta D / Geng, Zhi Zachary / Chen, Peng-Hsun Chase / Dubey, Gopal K / Sylvain, Lauralee D / Xu, Shiqing / Liu, Wenshe Ray

    Nucleic acids research

    2023  Band 51, Heft 13, Seite(n) 6566–6577

    Abstract: Using an amber suppression-based noncanonical amino acid (ncAA) mutagenesis approach, the chemical space in phage display can be significantly expanded for drug discovery. In this work, we demonstrate the development of a novel helper phage, CMa13ile40, ... ...

    Abstract Using an amber suppression-based noncanonical amino acid (ncAA) mutagenesis approach, the chemical space in phage display can be significantly expanded for drug discovery. In this work, we demonstrate the development of a novel helper phage, CMa13ile40, for continuous enrichment of amber obligate phage clones and efficient production of ncAA-containing phages. CMa13ile40 was constructed by insertion of a Candidatus Methanomethylophilus alvus pyrrolysyl-tRNA synthetase/PylT gene cassette into a helper phage genome. The novel helper phage allowed for a continuous amber codon enrichment strategy for two different libraries and demonstrated a 100-fold increase in packaging selectivity. CMa13ile40 was then used to create two peptide libraries containing separate ncAAs, Nϵ-tert-butoxycarbonyl-lysine and Nϵ-allyloxycarbonyl-lysine, respectively. These libraries were used to identify peptide ligands that bind to the extracellular domain of ZNRF3. Each selection showed differential enrichment of unique sequences dependent upon the ncAA used. Peptides from both selections were confirmed to have low micromolar affinity for ZNRF3 that was dependent upon the presence of the ncAA used for selection. Our results demonstrate that ncAAs in phages provide unique interactions for identification of unique peptides. As an effective tool for phage display, we believe that CMa13ile40 can be broadly applied to a wide variety of applications.
    Mesh-Begriff(e) Amino Acids/chemistry ; Amino Acyl-tRNA Synthetases/genetics ; Amino Acyl-tRNA Synthetases/metabolism ; Bacteriophages/enzymology ; Bacteriophages/genetics ; Cell Surface Display Techniques/methods ; Peptides/metabolism ; Drug Discovery
    Chemische Substanzen Amino Acids ; Amino Acyl-tRNA Synthetases (EC 6.1.1.-) ; Peptides
    Sprache Englisch
    Erscheinungsdatum 2023-06-09
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkad488
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Phage-assisted, active site-directed ligand evolution of a potent and selective histone deacetylase 8 inhibitor.

    Morse, Jared S / Sheng, Yan J / Hampton, Joshua Trae / Sylvain, Lauralee D / Das, Sukant / Alugubelli, Yugendar R / Chen, Peng-Hsun Chase / Yang, Kai S / Xu, Shiqing / Fierke, Carol A / Liu, Wenshe Ray

    Protein science : a publication of the Protein Society

    2022  Band 31, Heft 12, Seite(n) e4512

    Abstract: Phage-assisted, active site-directed ligand evolution (PADLE) is a recently developed technique that uses an amber codon-encoded noncanonical amino acid (ncAA) as an anchor to direct phage-displayed peptides to a target for an enhanced ligand ... ...

    Abstract Phage-assisted, active site-directed ligand evolution (PADLE) is a recently developed technique that uses an amber codon-encoded noncanonical amino acid (ncAA) as an anchor to direct phage-displayed peptides to a target for an enhanced ligand identification process. 2-Amino-8-oxodecanoic acid (Aoda) is a ketone-containing ncAA residue in the macrocyclic peptide natural product apicidin that is a pan-inhibitor of Zn
    Mesh-Begriff(e) Amino Acids/genetics ; Bacteriophages/genetics ; Bacteriophages/metabolism ; Catalytic Domain ; Codon, Terminator ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Histone Deacetylases/chemistry ; Ketones ; Ligands ; Peptides/chemistry ; Histone Deacetylase Inhibitors
    Chemische Substanzen Amino Acids ; Codon, Terminator ; Histone Deacetylases (EC 3.5.1.98) ; Ketones ; Ligands ; Peptides ; Histone Deacetylase Inhibitors
    Sprache Englisch
    Erscheinungsdatum 2022-11-12
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1106283-6
    ISSN 1469-896X ; 0961-8368
    ISSN (online) 1469-896X
    ISSN 0961-8368
    DOI 10.1002/pro.4512
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: A Novel Regioselective Approach to Cyclize Phage-Displayed Peptides in Combination with Epitope-Directed Selection to Identify a Potent Neutralizing Macrocyclic Peptide for SARS-CoV-2

    Hampton, Joshua Trae / Lalonde, Tyler J / Tharp, Jeffery M / Alugubelli, Yugendar R / Roundy, Christopher M / Hamer, Gabriel L / Xu, Shiqing / Liu, Wenshe R / Kurra, Yadagiri

    bioRxiv

    Abstract: Using the regioselective cyanobenzothiazole condensation reaction with the N-terminal cysteine and the chloroacetamide reaction with an internal cysteine, a phage-displayed macrocyclic 12-mer peptide library was constructed and subsequently validated. ... ...

    Abstract Using the regioselective cyanobenzothiazole condensation reaction with the N-terminal cysteine and the chloroacetamide reaction with an internal cysteine, a phage-displayed macrocyclic 12-mer peptide library was constructed and subsequently validated. Using this library in combination with iterative selections against two epitopes from the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein, macrocyclic peptides that strongly inhibit the interaction between the Spike RBD and ACE2, the human host receptor of SARS-CoV-2, were identified. The two epitopes were used instead of the Spike RBD to avoid selection of nonproductive macrocyclic peptides that bind RBD but do not directly inhibit its interactions with ACE2. Antiviral tests against SARS-CoV-2 showed that one macrocyclic peptide is highly potent against viral reproduction in Vero E6 cells with an EC50 value of 3.1 micromolar. The AlphaLISA-detected IC50 value for this macrocyclic peptide was 0.3 micromolar. The current study demonstrates that two kinetically-controlled reactions toward N-terminal and internal cysteines, respectively, are highly effective in the construction of phage-displayed macrocyclic peptides, and the selection based on the SARS-CoV-2 Spike epitopes is a promising methodology in the identification of peptidyl antivirals.
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2022-07-06
    Verlag Cold Spring Harbor Laboratory
    Dokumenttyp Artikel ; Online
    DOI 10.1101/2022.07.06.498864
    Datenquelle COVID19

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