Structure-Guided Discovery of the Novel Covalent Allosteric Site and Covalent Inhibitors of Fructose-1,6-Bisphosphate Aldolase to Overcome the Azole Resistance of

Allosteric Site Antifungal Agents / chemical synthesis Azoles / chemical synthesis Biofilms / drug effects Candida albicans / drug effects Candida parapsilosis / drug effects Drug Resistance, Fungal / drug effects Enzyme Inhibitors / chemical synthesis Fructose-Bisphosphate Aldolase / antagonists & inhibitors Fungal Proteins / antagonists & inhibitors Microbial Sensitivity Tests Molecular Structure Protein Binding Structure-Activity Relationship

Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
10 02 2022
Historique:
pubmed: 1 2 2022
medline: 19 2 2022
entrez: 31 1 2022
Statut: ppublish

Résumé

Fructose-1,6-bisphosphate aldolase (FBA) represents an attractive new antifungal target. Here, we employed a structure-based optimization strategy to discover a novel covalent binding site (C292 site) and the first-in-class covalent allosteric inhibitors of FBA from

Identifiants

DOI: 10.1021/acs.jmedchem.1c02102 PMID: 35099959
pubmed: 35099959
doi: 10.1021/acs.jmedchem.1c02102
doi:

Substances chimiques

Antifungal Agents 0
Azoles 0
Enzyme Inhibitors 0
Fungal Proteins 0
Fructose-Bisphosphate Aldolase EC 4.1.2.13

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

2656-2674

Auteurs

Wuqiang Wen (W)

Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China.

Hongxuan Cao (H)

Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China.

Yunyuan Huang (Y)

Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China.

Jie Tu (J)

School of Pharmacy, Second Military Medical University, Shanghai 200433, China.

Chen Wan (C)

Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China.

Jian Wan (J)

Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China.
ORCID: 0000-0003-4172-1392

Xinya Han (X)

Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China.

Han Chen (H)

Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China.

Jiaqi Liu (J)

Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China.

Li Rao (L)

Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China.
ORCID: 0000-0002-0780-6504

Chen Su (C)

National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai 201210, China.

Chao Peng (C)

National Facility for Protein Science in Shanghai, Zhangjiang Lab, Shanghai 201210, China.

Chunquan Sheng (C)

School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
ORCID: 0000-0001-9489-804X

Yanliang Ren (Y)

Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China.
ORCID: 0000-0001-8565-2152

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Classifications MeSH

questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Sites de fixation › Site allostérique › Structure-Guided Discovery of the Novel...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-infectieux › Antifongiques › Structure-Guided Discovery of the Novel...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Structure-Guided Discovery of the Novel...
questionsmedicales.fr › Phénomènes microbiologiques › Biofilms › Structure-Guided Discovery of the Novel...
questionsmedicales.fr › Eucaryotes › Champignons › Levures › Candida › Candida albicans › Structure-Guided Discovery of the Novel...
questionsmedicales.fr › Eucaryotes › Champignons › Levures › Candida › Candida parapsilosis › Structure-Guided Discovery of the Novel...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Résistance microbienne aux médicaments › Résistance des champignons aux médicaments › Structure-Guided Discovery of the Novel...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Structure-Guided Discovery of the Novel...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Lyases › Carbon-carbon lyases › Aldehyde-lyases › Fructose bisphosphate aldolase › Structure-Guided Discovery of the Novel...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines fongiques › Structure-Guided Discovery of the Novel...
questionsmedicales.fr › Techniques d'investigation › Évaluation préclinique de médicament › Tests de sensibilité microbienne › Structure-Guided Discovery of the Novel...
questionsmedicales.fr › Phénomènes chimiques › Structure moléculaire › Structure-Guided Discovery of the Novel...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › Structure-Guided Discovery of the Novel...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Relation structure-activité › Structure-Guided Discovery of the Novel...