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Cell penetrable, clickable and tagless activity-based probe of human cathepsin L.
Dana, Dibyendu; Garcia, Jeremy; Bhuiyan, Ashif I; Rathod, Pratikkumar; Joo, Laura; Novoa, Daniel A; Paroly, Suneeta; Fath, Karl R; Chang, Emmanuel J; Pathak, Sanjai K.
Afiliação
  • Dana D; Queens College of the City University of New York, Chemistry and Biochemistry Department, 65-30 Kissena Blvd, Flushing, NY 11367-1597, USA; Chemistry Doctoral Program, The Graduate Center of the City University of New York, 365 5th Ave, New York, NY 10016, USA.
  • Garcia J; Queens College of the City University of New York, Department of Biology, 65-30 Kissena Blvd, Flushing, NY 11367-1597, USA.
  • Bhuiyan AI; Queens College of the City University of New York, Chemistry and Biochemistry Department, 65-30 Kissena Blvd, Flushing, NY 11367-1597, USA; Biochemistry Doctoral Program, The Graduate Center of the City University of New York, 365 5th Ave, New York, NY 10016, USA.
  • Rathod P; York College of the City University of New York, Department of Chemistry, 94-20 Guy R. Brewer Blvd, Jamaica, NY 11451-0001, USA; Laguardia Community College, 31-10 Thomson Ave, Long Island City, NY 11101, USA.
  • Joo L; Queens College of the City University of New York, Chemistry and Biochemistry Department, 65-30 Kissena Blvd, Flushing, NY 11367-1597, USA.
  • Novoa DA; Queens College of the City University of New York, Chemistry and Biochemistry Department, 65-30 Kissena Blvd, Flushing, NY 11367-1597, USA.
  • Paroly S; Bard High School Early College Queens, 30-20 Thomson Avenue, Long Island City, NY 11101, USA.
  • Fath KR; Queens College of the City University of New York, Department of Biology, 65-30 Kissena Blvd, Flushing, NY 11367-1597, USA; Biochemistry Doctoral Program, The Graduate Center of the City University of New York, 365 5th Ave, New York, NY 10016, USA.
  • Chang EJ; York College of the City University of New York, Department of Chemistry, 94-20 Guy R. Brewer Blvd, Jamaica, NY 11451-0001, USA; Chemistry Doctoral Program, The Graduate Center of the City University of New York, 365 5th Ave, New York, NY 10016, USA; Biochemistry Doctoral Program, The Graduate Cente
  • Pathak SK; Queens College of the City University of New York, Chemistry and Biochemistry Department, 65-30 Kissena Blvd, Flushing, NY 11367-1597, USA; Chemistry Doctoral Program, The Graduate Center of the City University of New York, 365 5th Ave, New York, NY 10016, USA; Biochemistry Doctoral Program, The Gra
Bioorg Chem ; 85: 505-514, 2019 04.
Article em En | MEDLINE | ID: mdl-30802807
Human cathepsin L is a ubiquitously expressed endopeptidase and is known to play critical roles in a wide variety of cellular signaling events. Its overexpression has been implicated in numerous human diseases, including highly invasive forms of cancer. Inhibition of cathepsin L is therefore considered a viable therapeutic strategy. Unfortunately, several redundant and even opposing roles of cathepsin L have recently emerged. Selective cathepsin L probes are therefore needed to dissect its function in context-specific manner before significant resources are directed into drug discovery efforts. Herein, the development of a clickable and tagless activity-based probe of cathepsin L is reported. The probe is highly efficient, active-site directed and activity-dependent, selective, cell penetrable, and non-toxic to human cells. Using zebrafish model, we demonstrate that the probe can inhibit cathepsin L function in vivo during the hatching process. It is anticipated that the probe will be a highly effective tool in dissecting cathepsin L biology at the proteome levels in both normal physiology and human diseases, thereby facilitating drug-discovery efforts targeting cathepsin L.
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Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Sondas Moleculares / Catepsina L Limite: Animals / Humans Idioma: En Revista: Bioorg Chem Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Sondas Moleculares / Catepsina L Limite: Animals / Humans Idioma: En Revista: Bioorg Chem Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos