Highly Selective Binding and Inhibition of Pyr‐His‐Pro‐NH2 (TRH) Function using a Polypyridinyl Macrocyclic Receptor with an Amphiphilic Cavity. Issue 43 (8th July 2020)

• Record Type: Journal Article
• Authors: Hou, Chao‐Ping; Yang, Jian; Zhang, Lei; Ma, Zhen‐Hua; Li, Qian; Xiang, Jun‐Feng; Gong, Han‐Yuan
• Is Part Of: Chemistry. Volume 26:Issue 43(2020)
• Page Start: 9466
• Page End: 9470
• Publication Date: 2020-07-08
• Subjects: drug inhibition -- host–guest systems -- macrocyclic receptors -- molecular recognition -- adductive dosage; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202000888
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: 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‐NH2 ; 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. Abstract : In good form : The highly selective interaction between artificial polypyridinyl macrocycle and protirelin (TRH), induced unprecedented efficient TRH inhibition using only a small amount (0.003 molar equiv) of the macrocyclic receptor.