Dimerization of α-Conotoxins as a Strategy to Enhance the Inhibition of the Human α7 and α9α10 Nicotinic Acetylcholine Receptors.

Conotoxins / metabolism Humans Models, Molecular Nicotinic Antagonists / chemistry Protein Multimerization / drug effects Protein Subunits / antagonists & inhibitors Receptors, Nicotinic / metabolism alpha7 Nicotinic Acetylcholine Receptor / antagonists & inhibitors

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:
26 03 2020
Historique:
pubmed: 27 2 2020
medline: 4 9 2020
entrez: 27 2 2020
Statut: ppublish

Résumé

The affinity of α-conotoxins, a class of nicotinic acetylcholine receptor (nAChR) peptide inhibitors, can be enhanced by dendrimerization. It has been hypothesized that this improvement arose from simultaneous binding of the α-conotoxins to several spatially adjacent sites. We here engineered several α-conotoxin dimers using a linker length compatible between neighboring binding sites on the same receptor. Remarkably, the dimer of α-conotoxin PeIA compared to the monomer displayed an increase in potency by 11-fold (IC

Identifiants

DOI: 10.1021/acs.jmedchem.9b01536 PMID: 32101438
pubmed: 32101438
doi: 10.1021/acs.jmedchem.9b01536
doi:

Substances chimiques

Conotoxins 0
Nicotinic Antagonists 0
Protein Subunits 0
Receptors, Nicotinic 0
alpha7 Nicotinic Acetylcholine Receptor 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

2974-2985

Auteurs

Jiazhen Liang (J)

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266003, China.

Han-Shen Tae (HS)

Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong, Wollongong, New South Wales 2522, Australia.

Xiaoxiao Xu (X)

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266003, China.

Tao Jiang (T)

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266003, China.
ORCID: 0000-0002-6590-5041

David J Adams (DJ)

Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong, Wollongong, New South Wales 2522, Australia.
ORCID: 0000-0002-7030-2288

Rilei Yu (R)

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, China.
Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266003, China.
Innovation Center for Marine Drug Screening & Evaluation, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266003, China.
ORCID: 0000-0001-6625-2014

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Facteurs biologiques › Toxines biologiques › Venins › Venins de mollusque › Conotoxines › Dimerization of α-Conotoxins as a Strategy to...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Dimerization of α-Conotoxins as a Strategy to...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › Dimerization of α-Conotoxins as a Strategy to...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Agents neuromédiateurs › Agents cholinergiques › Antagonistes cholinergiques › Antagonistes nicotiniques › Dimerization of α-Conotoxins as a Strategy to...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Multimérisation de protéines › Dimerization of α-Conotoxins as a Strategy to...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Sous-unités de protéines › Dimerization of α-Conotoxins as a Strategy to...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs aux neuromédiateurs › Récepteurs cholinergiques › Récepteurs nicotiniques › Dimerization of α-Conotoxins as a Strategy to...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs aux neuromédiateurs › Récepteurs cholinergiques › Récepteurs nicotiniques › Récepteur nicotinique de l'acétylcholine alpha7 › Dimerization of α-Conotoxins as a Strategy to...