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Structure–Activity Relationship Study of T1R2/T1R3 Positive Allosteric Modulators and Evaluation of Their Enhancing Effect on Various Sweeteners
Author(s) -
Matsumoto Ryo,
Yamada Kei,
Nakazawa Masakazu,
Mori Suguru,
Kitajima Seiji
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202002159
Subject(s) - chemistry , allosteric regulation , tripeptide , sucralose , receptor , biochemistry , amino acid , food science
The sweet taste receptor T1R2/T1R3 belongs to the family of G protein coupled receptors and recognizes various sweet substances from small compounds to proteins. We have previously reported unnatural tripeptides that function as positive allosteric modulators (PAMs) of the T1R2/T1R3. The structures were classified into three parts—head, linker, and tail—as compared with known T1R2/T1R3 PAMs. Here, we conducted a structure–activity relationship study of the tail structure to further understand the structural features of the T1R2/T1R3 PAMs. Moreover, we evaluated the enhancing effect of these PAMs on various sweeteners. In conclusion, we found that both hydrophilic α‐amino acids and the hydrophobicity of the α‐amino acid side chain are important for enhancing activity for this receptor. These PAMs also showed the receptor enhancing activity against sugar‐like T1R2/T1R3 agonists such as sucrose, sucralose, and fructose.