Unnatural Tripeptides as Potent Positive Allosteric Modulators of T1R2/T1R3.
Journal
ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073
Informations de publication
Date de publication:
09 May 2019
09 May 2019
Historique:
received:
07
02
2019
accepted:
25
03
2019
entrez:
18
5
2019
pubmed:
18
5
2019
medline:
18
5
2019
Statut:
epublish
Résumé
T1R2/T1R3 belongs to G protein coupled receptors, which recognizes diverse natural and synthetic sweeteners. A novel class of positive allosteric modulators (PAMs) of T1R2/T1R3 was identified through high-throughput screening campaign. Comparing the structure of the potent compound with previously known PAM, we classified the structure of known PAM into three parts, defined as "head", "linker", and "tail". We then investigated the linker-tail structure. It was suggested by molecular docking models of T1R2/T1R3 that an amine that we introduced in the tail was the key for interaction with the receptor binding pocket. We thus synthesized various molecules and found unnatural tripeptide-PAMs, which potently enhance the sweetness of sucrose in sensory evaluation tests.
Identifiants
pubmed: 31098002
doi: 10.1021/acsmedchemlett.9b00051
pmc: PMC6511967
doi:
Types de publication
Journal Article
Langues
eng
Pagination
800-805Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
Références
Cell. 1999 Feb 19;96(4):541-51
pubmed: 10052456
Nature. 2000 Oct 26;407(6807):971-7
pubmed: 11069170
Cell. 2001 Aug 10;106(3):381-90
pubmed: 11509186
Nature. 2002 Mar 14;416(6877):199-202
pubmed: 11894099
Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4692-6
pubmed: 11917125
World Health Organ Tech Rep Ser. 2003;916:i-viii, 1-149, backcover
pubmed: 12768890
Pharmacol Ther. 2003 Jun;98(3):325-54
pubmed: 12782243
Public Health Nutr. 2004 Feb;7(1A):123-46
pubmed: 14972057
Chem Senses. 2006 Jul;31(6):573-80
pubmed: 16740645
Food Chem Toxicol. 2009 Feb;47(2):267-78
pubmed: 19041920
Am J Physiol Regul Integr Comp Physiol. 2009 Apr;296(4):R960-71
pubmed: 19211717
Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4746-51
pubmed: 20173092
Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4752-7
pubmed: 20173095
Trends Pharmacol Sci. 2011 Nov;32(11):631-6
pubmed: 21807420
J Acad Nutr Diet. 2012 May;112(5):739-58
pubmed: 22709780
Diabetes Care. 2012 Aug;35(8):1798-808
pubmed: 22778165
Nature. 1985 Oct 24-30;317(6039):717-9
pubmed: 2865680
Cell. 1995 Oct 20;83(2):195-206
pubmed: 7585937
Annu Rev Biophys Biomol Struct. 1994;23:319-48
pubmed: 7919785
Nature. 1993 Dec 9;366(6455):575-80
pubmed: 8255296
Nature. 1997 Mar 20;386(6622):239-46
pubmed: 9069281
Nature. 1998 Dec 17;396(6712):683-7
pubmed: 9872317