Total Synthesis of Covalent Cysteine Protease Inhibitor N-Desmethyl Thalassospiramide C and Crystallographic Evidence for Its Mode of Action.

Cathepsin K / chemistry Cysteine / chemistry Cysteine Proteinase Inhibitors / chemical synthesis Molecular Structure Serine Endopeptidases / chemistry

Journal

Organic letters
ISSN: 1523-7052
Titre abrégé: Org Lett
Pays: United States
ID NLM: 100890393

Informations de publication

Date de publication:
18 01 2019
Historique:
pubmed: 11 1 2019
medline: 30 7 2019
entrez: 11 1 2019
Statut: ppublish

Résumé

A total synthesis of N-desmethyl thalassospiramide C, a unique strained macrocyclic proteobacterial depsipeptide, enabled a detailed crystallographic study of its covalent complex with cathepsin K, a member of a medicinally important family of cysteine proteases. The study provides support for the mechanism of action, and the insight gained can be used for structure-based drug design targeting these calpain proteases.

Identifiants

DOI: 10.1021/acs.orglett.8b03821 PMID: 30628449
pubmed: 30628449
doi: 10.1021/acs.orglett.8b03821
doi:

Substances chimiques

Cysteine Proteinase Inhibitors 0
Serine Endopeptidases EC 3.4.21.-
protease C EC 3.4.21.-
Cathepsin K EC 3.4.22.38
Cysteine K848JZ4886

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Pagination

508-512

Auteurs

Jeremy Fournier (J)

Department of Chemistry and Biochemistry , University of California , Santa Barbara , California 93111 , United States.

Karen Chen (K)

Department of Chemistry and Biochemistry , University of California , Santa Barbara , California 93111 , United States.

Artur K Mailyan (AK)

Department of Chemistry and Biochemistry , University of California , Santa Barbara , California 93111 , United States.

Jeffrey J Jackson (JJ)

Department of Chemistry and Biochemistry , University of California , Santa Barbara , California 93111 , United States.

Brad O Buckman (BO)

Blade Therapeutics , 442 Littlefield Avenue , South San Francisco , California 94080 , United States.

Kumar Emayan (K)

Bayside Pharma , 2600 Hilltop Drive , Richmond , California 94806 , United States.

Shendong Yuan (S)

Bayside Pharma , 2600 Hilltop Drive , Richmond , California 94806 , United States.

Ravi Rajagopalan (R)

Blade Therapeutics , 442 Littlefield Avenue , South San Francisco , California 94080 , United States.

Shawn Misialek (S)

Blade Therapeutics , 442 Littlefield Avenue , South San Francisco , California 94080 , United States.

Marc Adler (M)

ChemPartner , 280 Utah Avenue Suite 100 , South San Francisco , California 94080 , United States.

Michael Blaesse (M)

Proteros Biostructures GmbH , Bunsenstraße 7 a , 82152 Planegg-Martinsried , Germany.

Andreas Griessner (A)

Proteros Biostructures GmbH , Bunsenstraße 7 a , 82152 Planegg-Martinsried , Germany.

Armen Zakarian (A)

Department of Chemistry and Biochemistry , University of California , Santa Barbara , California 93111 , United States.
ORCID: 0000-0002-9120-1232

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Classifications MeSH

questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Endopeptidases › Cysteine endopeptidases › Cathepsine K › Total Synthesis of Covalent Cysteine Protease...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés soufrés › Cystéine › Total Synthesis of Covalent Cysteine Protease...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibiteurs de protéases › Inhibiteurs de la cystéine protéinase › Total Synthesis of Covalent Cysteine Protease...
questionsmedicales.fr › Phénomènes chimiques › Structure moléculaire › Total Synthesis of Covalent Cysteine Protease...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Protéases à sérine › Serine endopeptidases › Total Synthesis of Covalent Cysteine Protease...