Identification of peptidomimetics as novel chemical probes modulating fibroblast growth factor 14 (FGF14) and voltage-gated sodium channel 1.6 (Nav1.6) protein-protein interactions.

Dose-Response Relationship, Drug Fibroblast Growth Factors / antagonists & inhibitors Humans Molecular Probes / chemical synthesis Molecular Structure NAV1.6 Voltage-Gated Sodium Channel / chemistry Oligopeptides / chemical synthesis Peptidomimetics / chemical synthesis Protein Binding / drug effects Structure-Activity Relationship
Chemical probes Fibroblast growth factor Protein-protein interactions Split-luciferase complementation assay Voltage-gated sodium channels

Journal

Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377

Informations de publication

Date de publication:
01 02 2019
Historique:
received: 19 11 2018
revised: 11 12 2018
accepted: 13 12 2018
pubmed: 28 12 2018
medline: 18 12 2019
entrez: 28 12 2018
Statut: ppublish

Résumé

The voltage-gated sodium (Nav) channel is the molecular determinant of action potential in neurons. Protein-protein interactions (PPI) between the intracellular Nav1.6 C-tail and its regulatory protein fibroblast growth factor 14 (FGF14) provide an ideal and largely untapped opportunity for development of neurochemical probes. Based on a previously identified peptide FLPK, mapped to the FGF14:FGF14 PPI interface, we have designed and synthesized a series of peptidomimetics with the intent of increasing clogP values and improving cell permeability relative to the parental lead peptide. In-cell screening using the split-luciferase complementation (LCA) assay identified ZL0177 (13) as the most potent inhibitor of the FGF14:Nav1.6 channel complex assembly with an apparent IC

Identifiants

DOI: 10.1016/j.bmcl.2018.12.031 PMID: 30587448 PMC: PMC6748043
pubmed: 30587448
pii: S0960-894X(18)30977-6
doi: 10.1016/j.bmcl.2018.12.031
pmc: PMC6748043
mid: NIHMS1049553
pii:
doi:

Substances chimiques

Molecular Probes 0
NAV1.6 Voltage-Gated Sodium Channel 0
Oligopeptides 0
Peptidomimetics 0
SCN8A protein, human 0
fibroblast growth factor 14 0
Fibroblast Growth Factors 62031-54-3

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

413-419

Subventions

Organisme : NIDA NIH HHS
ID : P30 DA028821
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG051131
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM089657
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH095995
Pays : United States
Organisme : NIH HHS
ID : S10 OD023576
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH111107
Pays : United States

Informations de copyright

Copyright © 2018 Elsevier Ltd. All rights reserved.

Références

Assay Drug Dev Technol. 2012 Apr;10(2):148-60
pubmed: 22364545
Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8963-8
pubmed: 9671787
J Physiol. 2005 Nov 15;569(Pt 1):179-93
pubmed: 16166153
Am J Hum Genet. 2001 Jun;68(6):1327-32
pubmed: 11359211
J Pharmacol Exp Ther. 2011 Jul;338(1):100-13
pubmed: 21487071
Exp Physiol. 2014 Jan;99(1):35-51
pubmed: 24097157
Mol Cell Neurosci. 2009 Oct;42(2):90-101
pubmed: 19465131
ACS Chem Neurosci. 2018 May 16;9(5):976-987
pubmed: 29359916
PLoS One. 2015 Feb 06;10(2):e0117246
pubmed: 25659151
J Neurosci. 2003 Aug 20;23(20):7577-85
pubmed: 12930796
Arch Neurol. 2009 Jan;66(1):21-6
pubmed: 19139296
Brain Res Rev. 2009 Apr;60(1):65-83
pubmed: 19150627
Pharm Res. 2011 May;28(5):962-77
pubmed: 21052797
J Chem Inf Model. 2012 Jun 25;52(6):1621-36
pubmed: 22621168
J Biol Chem. 2013 Jul 5;288(27):19370-85
pubmed: 23640885
J Phys Chem B. 2017 May 25;121(20):5228-5237
pubmed: 28453293
J Biol Chem. 2016 May 20;291(21):11268-84
pubmed: 26994141
Eur J Hum Genet. 2015 Oct;23(10):1434
pubmed: 26376683
Neuron. 2005 Jan 20;45(2):233-44
pubmed: 15664175
Mol Cell Neurosci. 2002 Sep;21(1):63-80
pubmed: 12359152
J Neurosci. 2007 Oct 31;27(44):12033-44
pubmed: 17978045
J Med Chem. 2015 Sep 24;58(18):7093-118
pubmed: 25927480
J Med Chem. 2005 Feb 10;48(3):805-11
pubmed: 15689164
Cell. 1995 Mar 10;80(5):805-11
pubmed: 7889574
Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18177-82
pubmed: 16326807
J Am Coll Cardiol. 2003 Feb 19;41(4):643-52
pubmed: 12598077
J Biol Chem. 1999 Nov 12;274(46):32647-54
pubmed: 10551819
Proc Natl Acad Sci U S A. 2015 Oct 6;112(40):12528-33
pubmed: 26392562
J Physiol. 1998 May 1;508 ( Pt 3):647-57
pubmed: 9518722
Orphanet J Rare Dis. 2015 Sep 30;10:127
pubmed: 26419464
J Biol Chem. 2009 Jun 26;284(26):17883-96
pubmed: 19406745
CNS Neurol Disord Drug Targets. 2014;13(9):1559-70
pubmed: 25426956

Auteurs

Zhiqing Liu (Z)

Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Blvd, Galveston, Galveston, TX 77555, United States.

Paul Wadsworth (P)

Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Blvd, Galveston, Galveston, TX 77555, United States.

Aditya K Singh (AK)

Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Blvd, Galveston, Galveston, TX 77555, United States.

Haiying Chen (H)

Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Blvd, Galveston, Galveston, TX 77555, United States.

Pingyuan Wang (P)

Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Blvd, Galveston, Galveston, TX 77555, United States.

Oluwarotimi Folorunso (O)

Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Blvd, Galveston, Galveston, TX 77555, United States.

Pietro Scaduto (P)

Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Blvd, Galveston, Galveston, TX 77555, United States.

Syed R Ali (SR)

Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Blvd, Galveston, Galveston, TX 77555, United States.

Fernanda Laezza (F)

Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Blvd, Galveston, Galveston, TX 77555, United States. Electronic address: felaezza@utmb.edu.

Jia Zhou (J)

Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Blvd, Galveston, Galveston, TX 77555, United States. Electronic address: jizhou@utmb.edu.

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 › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes toxicologiques › Relation dose-effet des médicaments › Identification of peptidomimetics as novel...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Facteurs de croissance fibroblastique › Identification of peptidomimetics as novel...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Identification of peptidomimetics as novel...
questionsmedicales.fr › Actions chimiques et utilisations › Utilisations spécialisées de produits chimiques › Produits chimiques de laboratoire › Sondes moléculaires › Identification of peptidomimetics as novel...
questionsmedicales.fr › Phénomènes chimiques › Structure moléculaire › Identification of peptidomimetics as novel...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Canaux sodiques voltage-dépendants › Canal sodique voltage-dépendant NAV1.6 › Identification of peptidomimetics as novel...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Oligopeptides › Identification of peptidomimetics as novel...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Peptidomimétiques › Identification of peptidomimetics as novel...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › Identification of peptidomimetics as novel...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Relation structure-activité › Identification of peptidomimetics as novel...