6305-38-0Relevant articles and documents
Synthesis of water soluble and multi-responsive selenopolypeptides via ring-opening polymerization of N-carboxyanhydrides
Wu, Guangqi,Ge, Chenglong,Liu, Xingyi,Wang, Shuo,Wang, Letian,Yin, Lichen,Lu, Hua
supporting information, p. 7860 - 7863 (2019/07/12)
We report here the synthesis of water soluble selenopolypeptides via the ring-opening polymerization of N-carboxyanhydrides. The oligoethylene glycol-bearing selenopolypeptides are thermally responsive in aqueous solutions with tunable lower critical solution temperatures. The polymers can also undergo rapid and reversible helix-coil transitions upon responding to the added redox cycle.
Small Molecule Inhibitors of the PCSK9·LDLR Interaction
Taechalertpaisarn, Jaru,Zhao, Bosheng,Liang, Xiaowen,Burgess, Kevin
supporting information, p. 3242 - 3249 (2018/03/13)
The protein-protein interaction between proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein receptor (LDLR) is a relatively new, and extremely important, validated therapeutic target for treatment and prevention of heart disease. Experts in the area agree that the first small molecules to disrupt PCSK9·LDLR would represent a milestone in this field, yet few credible leads have been reported. This paper describes how side-chain orientations in preferred conformations of carefully designed chemotypes were compared with LDLR side chains at the PCSK9·LDLR interface to find molecules that would mimic interface regions of LDLR. This approach is an example of the procedure called EKO (Exploring Key Orientations). The guiding hypothesis on which EKO is based is that good matches indicate the chemotypes bearing the same side chains as the protein at the sites of overlay have the potential to disrupt the parent protein-protein interaction. In the event, the EKO procedure and one round of combinatorial fragment-based virtual docking led to the discovery of seven compounds that bound PCSK9 (SPR and ELISA) and had a favorable outcome in a cellular assay (hepatocyte uptake of fluorescently labeled low-density lipoprotein particles) and increased the expression LDLR on hepatocytes in culture. Three promising hit compounds in this series had dissociation constants for PCSK9 binding in the 20-40 μM range, and one of these was modified with a photoaffinity label and shown to form a covalent conjugate with PCSK9 on photolysis.
Design, synthesis and activity evaluation study of novel substituted N-sulfonyl homoserine lactone derivatives as bacterial quorum sensing inhibitors
Sun, Qi,Zhao, Mingming,Liang, Jingwei,Xiao, Junhai,Meng, Fanhao
, p. 3345 - 3353 (2017/11/16)
A novel series of N-sulfonyl homoserine lactone derivatives 7a–7m has been designed, synthesized, and evaluated for quorum sensing inhibitory activities through the violacein inhibition in Chromobacterium violaceum CV026. Compound 7e displayed the high level of inhibitory activity among all the compounds synthesized. Studies of structure-activity relationship indicated that compounds with thiophene group in side chain showed better activity than those substituted by furan, pyrrole, pyridyl, and phenethyl group. Thiophene substituted compounds which connected electron withdrawing group exhibited better inhibitory activity relate to those connected electron donating group. Further analysis indicated that compound bearing an electron withdrawing substituent at the position 2 of their thiophene ring exhibited superior activity against violacein production to those bearing the substituent at the position 3 and 4. Compound 7e in particular, with IC50 value of 6.19 μM, were identified as promising lead compounds for further development.
