ml9b00051_si_001.pdf (978.37 kB)
Unnatural Tripeptides as Potent Positive Allosteric Modulators of T1R2/T1R3
journal contribution
posted on 2019-03-25, 00:00 authored by Kei Yamada, Masakazu Nakazawa, Kayo Matsumoto, Uno Tagami, Takatsugu Hirokawa, Keisuke Homma, Suguru Mori, Ryo Matsumoto, Wakana Saikawa, Seiji KitajimaT1R2/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.