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Highly Selective Binding and Inhibition of Pyr‐His‐Pro‐NH 2 (TRH) Function using a Polypyridinyl Macrocyclic Receptor with an Amphiphilic Cavity
Author(s) -
Hou ChaoPing,
Yang Jian,
Zhang Lei,
Ma ZhenHua,
Li Qian,
Xiang JunFeng,
Gong HanYuan
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202000888
Subject(s) - chemistry , amphiphile , drug , combinatorial chemistry , membrane , stereochemistry , function (biology) , solid state , biophysics , biochemistry , organic chemistry , biology , polymer , pharmacology , evolutionary biology , copolymer
Macrocycle, cyclo[4] [(1,3‐(4,6)‐dimethylbezene)[4](2,6‐(3,5)‐dimethylpyridine ( B4P4 ), shows highly selective binding affinity with protirelin (Pyr‐His‐Pro‐NH 2 ; TRH) among the tested 26 drug or drug adductive substrates. The stable complexation in a 1:1 manner was fully characterized in solution, gas phase, and solid state study. Furthermore, B4P4 acts as an efficient TRH inhibitor even at [macrocycle]:[drug] <1:300, both in membrane transport and cellar incubation. The current work provides an unprecedented strategy for macrocycles to be efficiently used in drug target therapy.