至今,GenScript的服务及产品已被Cell, Nature, Science, PNAS等1300多家生物医药类杂志引用近万次,处于行业领先水平。NIH、哈佛、耶鲁、斯坦福、普林斯顿、杜克大学等约400家全球著名机构使用GenScript的基因合成、多肽服务、抗体服务和蛋白服务等成功地发表科研成果,再次证明GenScript 有能力帮助业内科学家Make research easy.

Exploring the molecular determinants for subtypeselectivity of 2‑amino‑1,4,5,6‑ tetrahydropyrimidine‑5‑carboxylic acid analogs as betaine/GABA transporter 1 (BGT1) substrateinhibitors

Sci Rep. 2020-08; 
Stefanie Kickinger , Anas Al-Khawaja , Anne Stæhr Haugaard , Maria E K Lie , Francesco Bavo , Rebekka Löffler , Maria Damgaard , Gerhard F Ecker , Bente Frølund , Petrine Wellendorph
Products/Services Used Details Operation
Mutagenesis Services hBGT1 E52Y, E52A, C301S, Q299L+E52A, and Q299L+E52Y were synthetized by Genscript (Piscataway, NJ, USA) Get A Quote

摘要

We have previously identified 2-amino-1,4,5,6-tetrahydropyrimidine-5-carboxylic acid (ATPCA) as the most potent substrate-inhibitor of the betaine/GABA transporter 1 (BGT1) (IC50 2.5 µM) reported to date. Herein, we characterize the binding mode of 20 novel analogs and propose the molecular determinants driving BGT1-selectivity. A series of N1-, exocyclic-N-, and C4-substituted analogs was synthesized and pharmacologically characterized in radioligand-based uptake assays at the four human GABA transporters (hGATs) recombinantly expressed in mammalian cells. Overall, the analogs retained subtype-selectivity for hBGT1, though with lower inhibitory activities (mid to high micromolar IC50 values) compared to ATPCA... More

关键词