70260-95-6Relevant articles and documents
Bioconjugation with Thiols by Benzylic Substitution
Watanabe, Kenji,Ohshima, Takashi
supporting information, p. 3959 - 3964 (2018/02/22)
A benzylic substitution of 3-indolyl(hydroxyl)acetate derivatives with thiols proceeded specifically in the presence of amino, carboxy, and phosphate groups in weakly acidic aqueous solutions under nearly physiological condition, while no reaction occurred at pH over 7. Kinetic studies revealed that the reaction followed second-order kinetics (first-order in the reactant and first-order in thiol) in contrast with the SN1 mechanism of common benzylic substitution of alcohols. The utility of the present method for functionalization of biomacromolecules was demonstrated using several model proteins, such as lysozyme, insulin, trypsin, and serum albumin. The catalytic bioactivity of lysozyme in lysis of Micrococcus lysodeikticus cells was completely retained after the modification.
Structural basis for the improved potency of Peroxisome Proliferator-Activated Receptor (PPAR) agonists
Peng, Yi-Hui,Coumar, Mohane Selvaraj,Leou, Jiun-Shyang,Wu, Jian-Sung,Shiao, Hui-Yi,Lin, Chia-Hui,Lin, Wen-Hsing,Lien, Tzu Wen,Chen, Xin,Hsu, John T.-A.,Chao, Yu-Sheng,Huang, Chien-Fu,Lyu, Ping-Chiang,Hsieh, Hsing-Pang,Wu, Su-Ying
body text, p. 1707 - 1716 (2012/01/02)
The need to develop safer and more effective antidiabetic drugs is essential owing to the growth worldwide of the diabetic population. Targeting the PPAR receptor is one strategy for the treatment of diabetes; the PPAR agonists rosiglitazone and pioglitazone are already on the market. Here we report the identification of a potent PPAR agonist, 15, whose PPARγ activation was more than 20 times better than that of rosiglitazone. Compound 15 was designed to incorporate an indole head with a carboxylic acid group, and 4-phenylbenzophenone tail to achieve a PPARγ EC50 of 10 nm. Compound 15 showed the most potent PPARγ agonist activity among the compounds we investigated. To gain molecular insight into the improved potency of 15, a structural biology study and binding energy calculations were carried out. Superimposition of the X-ray structures of 15 and agonist 10 revealed that, even though they have the same indole head part, they adopt different conformations. The head part of 15 showed stronger interactions toward PPARγ; this could be due to the presence of the novel tail part 4-phenylbenzophenone, which could enhance the binding efficiency of 15 to PPARγ.
Novel indole-based peroxisome proliferator-activated receptor agonists: Design, SAR, structural biology, and biological activities
Mahindroo, Neeraj,Huang, Chien-Fu,Peng, Yi-Huei,Wang, Chiung-Chiu,Liao, Chun-Chen,Lien, Tzu-Wen,Chittimalla, Santhosh Kumar,Huang, Wei-Jan,Chai, Chia-Hua,Prakash, Ekambaranellore,Chen, Ching-Ping,Hsu, Tsu-An,Peng, Cheng-Hung,Lu, I-Lin,Lee, Ling-Hui,Chang, Yi-Wei,Chen, Wei-Cheng,Chou, Yu-Chen,Chen, Chiung-Tong,Goparaju, Chandra M. V.,Chen, Yuan-Shou,Lan, Shih-Jung,Yu, Ming-Chen,Chen, Xin,Chao, Yu-Sheng,Wu, Su-Ying,Hsieh, Hsing-Pang
, p. 8194 - 8208 (2007/10/03)
The synthesis and structure-activity relationship studies of novel indole derivatives as peroxisome proliferator-activated receptor (PPAR) agonists are reported. Indole, a druglike scaffold, was studied as a core skeleton for the acidic head part of PPAR
