Search results for: Jordan Tang

Items from 1 to 20 out of 49 results

article

Cardosin A endocytosis mediated by integrin leads to lysosome leakage and apoptosis of epithelial cells

Hao Wu, Pedro Castanheira, Carlos Faro, Jordan Tang

Proteins: Structure, Function, and Bioinformatics > 87 > 6 > 502 - 511

Cardosin A is an aspartic protease present in large amount in the pistils of cardoon flowers. This protease is known to contain an ‐Arg‐Gly‐Asp‐ (RGD) motif located on the molecular surface. In this study, we found that isolated recombinant cardosin A attached to human epithelial cells A549, mediated by the binding of its RGD motif to cell surface integrins. The cell bound cardosin A was internalized...

article

Design, synthesis, X-ray studies, and biological evaluation of novel BACE1 inhibitors with bicyclic isoxazoline carboxamides as the P3 ligand

Arun K. Ghosh, Koena Ghosh, Margherita Brindisi, Emma K. Lendy, more

Bioorganic & Medicinal Chemistry Letters > 2018 > 28 > 15 > 2605-2610

We describe the design, synthesis, X-ray studies, and biological evaluation of novel BACE1 inhibitors containing bicyclic isoxazoline carboxamides as the P3 ligand in combination with methyl cysteine, methylsulfonylalanine and Boc-amino alanine as P2 ligands. Inhibitor 3a displayed a BACE1 K_i value of 10.9 nM and EC₅₀ of 343 nM. The X-ray structure of 3a bound to the active site of BACE1 was determined...

article

Design, synthesis, and X-ray structural studies of BACE-1 inhibitors containing substituted 2-oxopiperazines as P1′-P2′ ligands

Arun K. Ghosh, Margherita Brindisi, Yu-Chen Yen, Emilio L. Cárdenas, more

Bioorganic & Medicinal Chemistry Letters > 2017 > 27 > 11 > 2432-2438

We report the design and synthesis of a series of BACE1 inhibitors incorporating mono- and bicyclic 6-substituted 2-oxopiperazines as novel P1′ and P2′ ligands and isophthalamide derivative as P2-P3 ligands. Among mono-substituted 2-oxopiperazines, inhibitor 5a with N-benzyl-2-oxopiperazine and isophthalamide showed potent BACE1 inhibitory activity (K_i=2nM). Inhibitor 5g, with N-benzyl-2-oxopiperazine...

article

Structure-based design, synthesis and biological evaluation of novel β-secretase inhibitors containing a pyrazole or thiazole moiety as the P3 ligand

Arun K. Ghosh, Margherita Brindisi, Yu-Chen Yen, Xiaoming Xu, more

Bioorganic & Medicinal Chemistry Letters > 2015 > 25 > 3 > 668-672

We describe structure-based design, synthesis, and biological evaluation of a series of novel inhibitors bearing a pyrazole (compounds 3a–h) or a thiazole moiety (compounds 4a–e) as the P3 ligand. We have also explored Boc-β-amino-l-alanine as a novel P2 ligand. A number of inhibitors have displayed β-secretase inhibitory potency. Inhibitor 4c has shown potent BACE1 inhibitory activity, K _i ...

article

Expression and processing of fluorescent fusion proteins of amyloid precursor protein (APP)

Kathleen Coughlan, Xiangping Huang, Xiangyuan He, Charlotte H.Y. Chung, more

BBA - Molecular Cell Research > 2013 > 1833 > 6 > 1562-1571

Processing of β-amyloid precursor protein (APP) by β- and γ-secretases in neurons produces amyloid-β (Aβ), whose excess accumulation leads to Alzheimer's disease (AD). Knowledge on subcellular trafficking pathways of APP and its fragments is important for the understanding of AD pathogenesis. We designed fusion proteins comprising a C-terminal fragment of APP (app) and fluorescent proteins GFP (G)...

article

Structure-based design, synthesis, and biological evaluation of dihydroquinazoline-derived potent β-secretase inhibitors

Arun K. Ghosh, Satyendra Pandey, Sudhakar Gangarajula, Sarang Kulkarni, more

Bioorganic & Medicinal Chemistry Letters > 2012 > 22 > 17 > 5460-5465

Structure-based design, synthesis, and biological evaluation of a series of dihydroquinazoline-derived β-secretase inhibitors incorporating thiazole and pyrazole-derived P2-ligands are described. We have identified inhibitor 4f which has shown potent enzyme inhibitory (K _i =13nM) and cellular (IC ₅₀ =21nM in neuroblastoma cells) assays. A model of 4f was created based upon the X-ray...

article

Inhibition of anthrax lethal factor: lability of hydroxamate as a chelating group

Feng Li, Irina Chvyrkova, Simon Terzyan, Nancy Wakeham, more

Applied Microbiology and Biotechnology > 2012 > 94 > 4 > 1041-1049

The metalloprotease activity of lethal factor (LF) from Bacillus anthracis (B. anthracis) is a main source of toxicity in the lethality of anthrax infection. Thus, the understanding of the enzymatic activity and inhibition of B. anthracis LF is of scientific and clinical interests. We have designed, synthesized, and studied a peptide inhibitor of LF, R9LF-1, with the structure NH₂–(d-Arg)₉–Val–Leu–Arg–CO–NHOH...

article

Developing β‐secretase inhibitors for treatment of Alzheimer’s disease

Arun K. Ghosh, Margherita Brindisi, Jordan Tang

Journal of Neurochemistry > 120 > s1 > 71 - 83

J. Neurochem. (2012) 120 (Suppl. 1), 71–83. Abstractβ‐Secretase (memapsin 2; BACE‐1) is the first protease in the processing of amyloid precursor protein leading to the production of amyloid‐β (Aβ) in the brain. It is believed that high levels of brain Aβ are responsible for the pathogenesis of Alzheimer’s disease (AD). Therefore, β‐secretase is a major therapeutic target for the development of inhibitor...

article

Subsite specificity of anthrax lethal factor and its implications for inhibitor development

Feng Li, Simon Terzyan, Jordan Tang

Biochemical and Biophysical Research Communications > 2011 > 407 > 2 > 400-405

The lethal factor of Bacillus anthracis is a major factor for lethality of anthrax infection by this bacterium. With the aid of the protective antigen, lethal factor gains excess to the cell cytosol where it manifests toxicity as a metalloprotease. For better understanding of its specificity, we have determined its residue preferences of 19 amino acids in six subsites (from P3 to P3′) as relative...

article

Design, Synthesis, Protein−Ligand X-ray Structure, and Biological Evaluation of a Series of Novel Macrocyclic Human Immunodeficiency Virus-1 Protease Inhibitors to Combat Drug Resistance

Arun K. Ghosh, Sarang Kulkarni, David D. Anderson, Lin Hong, more

Journal of Medicinal Chemistry > 2009 > 52 > 23 > 7689 - 7705

article

In vivo efficacy of BACE-1 inhibitor CTS21166 (ASP1702) in rat CNS compartments

Jeremy Yu, Gerald Koelsch, Aiqun Li, Robert T. Turner, more

Alzheimer's & Dementia > 2009 > 5 > 4(S) > P430-P431

article

γ-secretase processing of APLP1 leads to the production of a p3-like peptide that does not aggregate and is not toxic to neurons

Aedín M. Minogue, Adam K. Stubbs, Carlo Sala Frigerio, Barry Boland, more

Brain Research > 2009 > 1262 > Complete > 89-99

The amyloid precursor-like protein-1 (APLP1) is a member of a protein family that includes the Alzheimer's disease-associated amyloid precursor protein (APP). While much is known about the proteolytic processing of APP, fewer details are available about APLP1. Using Chinese hamster ovarian cells stably transfected with human APLP1 and a novel juxtamembrane anti-APLP1 antibody, we demonstrate the detection...

article

β-Secretase as a Therapeutic Target for Alzheimer's Disease

Arun K. Ghosh, Sandra Gemma, Jordan Tang

Neurotherapeutics > 2008 > 5 > 3 > 399-408

β-Secretase (memapsin 2, BACE1) is an attractive target for the development of inhibitor drugs to treat Alzheimer's disease (AD). Not only does this protease function at the first step in the pathway leading to the production of amyloid-β (Aβ), its gene deletion produces only mild phenotypes. In addition, β-secretase is an aspartic protease whose mechanism and inhibition are well known. The development...

article

P2-323: Memapsin 2 (beta-secretase, BACE) immunization as specific and safe therapy for Alzheimer's disease

Wan-Pin Chang, Huining Da, Xiangping Huang, Deborah Downs, more

Alzheimer's & Dementia: The Journal of the Alzheimer's Association > 2008 > 4 > 4 Supplement > T467

article

Potent memapsin 2 (β-secretase) inhibitors: Design, synthesis, protein-ligand X-ray structure, and in vivo evaluation

Arun K. Ghosh, Nagaswamy Kumaragurubaran, Lin Hong, Sarang Kulkarni, more

Bioorganic & Medicinal Chemistry Letters > 2008 > 18 > 3 > 1031-1036

Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic β-secretase inhibitors incorporating hydroxyethylamine isosteres are described. We have identified inhibitor 24 which has shown exceedingly potent activity in memapsin 2 enzyme inhibitory (K _i 1.8nM) and cellular (IC ₅₀ =1nM in Chinese hamster ovary cells) assays. Inhibitor 24 has also shown...

article

β-Secretase as a therapeutic target for Alzheimer’s disease

Arun K. Ghosh, Sandra Gemma, Jordan Tang

Neurotherapeutics > 2008 > 5 > 3 > 399-408

Summary β-Secretase (memapsin 2, BACE1) is an attractive target for the development of inhibitor drugs to treat Alzheimer’s disease (AD). Not only does this protease function at the first step in the pathway leading to the production of amyloid-β (Aβ), its gene deletion produces only mild phenotypes. In addition, β-secretase is an aspartic protease whose mechanism and inhibition are well known. The...

article

Design, Synthesis, and X-ray Structure of Potent Memapsin 2 (β-Secretase) Inhibitors with Isophthalamide Derivatives as the P ₂ _- P ₃ -Ligands

Arun K. Ghosh, Nagaswamy Kumaragurubaran, Lin Hong, Sarang S. Kulkarni, more

Journal of Medicinal Chemistry > 2007 > 50 > 10 > 2399 - 2407

article

Memapsin 2 (beta-secretase, BACE) immunization as therapy for Alzheimer’s disease

Wan-Pin Chang, Gerald Koelsch, Deborah Downs, Kar-Ming Fung, more

Alzheimer's & Dementia: The Journal of the Alzheimer's Association > 2006 > 2 > 3 Supplement > S20-S21

article

APLP1-derived peptides do not undergo rapid fibrillogenesis

Aedin M. Minogue, Julia V. Fadeeva, Jordan Tang, Wilma Wasco, more

Alzheimer's & Dementia: The Journal of the Alzheimer's Association > 2006 > 2 > 3 Supplement > S478

article

Design, Synthesis and X-ray Structure of Protein−Ligand Complexes: Important Insight into Selectivity of Memapsin 2 (β-Secretase) Inhibitors

Arun K. Ghosh, Nagaswamy Kumaragurubaran, Lin Hong, Hui Lei, more

Journal of the American Chemical Society > 2006 > 128 > 16 > 5310 - 5311

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Search results for: Jordan Tang

Cardosin A endocytosis mediated by integrin leads to lysosome leakage and apoptosis of epithelial cells

Design, synthesis, X-ray studies, and biological evaluation of novel BACE1 inhibitors with bicyclic isoxazoline carboxamides as the P3 ligand

Design, synthesis, and X-ray structural studies of BACE-1 inhibitors containing substituted 2-oxopiperazines as P1′-P2′ ligands

Structure-based design, synthesis and biological evaluation of novel β-secretase inhibitors containing a pyrazole or thiazole moiety as the P3 ligand

Expression and processing of fluorescent fusion proteins of amyloid precursor protein (APP)

Structure-based design, synthesis, and biological evaluation of dihydroquinazoline-derived potent β-secretase inhibitors

Inhibition of anthrax lethal factor: lability of hydroxamate as a chelating group

Developing β‐secretase inhibitors for treatment of Alzheimer’s disease

Subsite specificity of anthrax lethal factor and its implications for inhibitor development

Design, Synthesis, Protein−Ligand X-ray Structure, and Biological Evaluation of a Series of Novel Macrocyclic Human Immunodeficiency Virus-1 Protease Inhibitors to Combat Drug Resistance

In vivo efficacy of BACE-1 inhibitor CTS21166 (ASP1702) in rat CNS compartments

γ-secretase processing of APLP1 leads to the production of a p3-like peptide that does not aggregate and is not toxic to neurons

β-Secretase as a Therapeutic Target for Alzheimer's Disease

P2-323: Memapsin 2 (beta-secretase, BACE) immunization as specific and safe therapy for Alzheimer's disease

Potent memapsin 2 (β-secretase) inhibitors: Design, synthesis, protein-ligand X-ray structure, and in vivo evaluation

β-Secretase as a therapeutic target for Alzheimer’s disease

Design, Synthesis, and X-ray Structure of Potent Memapsin 2 (β-Secretase) Inhibitors with Isophthalamide Derivatives as the P ₂ _- P ₃ -Ligands

Memapsin 2 (beta-secretase, BACE) immunization as therapy for Alzheimer’s disease

APLP1-derived peptides do not undergo rapid fibrillogenesis

Design, Synthesis and X-ray Structure of Protein−Ligand Complexes: Important Insight into Selectivity of Memapsin 2 (β-Secretase) Inhibitors

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