Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
Bioorg Chem. 2015 Dec;63:53-7. doi: 10.1016/j.bioorg.2015.09.007. Epub 2015 Sep 30.
Strained unusual amino acid derived tetrapeptides were synthesized as mimics of GLYX-13, a clinical candidate for neuroprotective and anti-depressant properties, were studied. The synthesized compounds were screened for neurite growth and anti-depressant properties in vitro and in vivo respectively comparing with the parent GLYX-13 compound. Neurite growth property was assessed by neurite length and anti-depressant property by percentage of immobility in forced swim test, a behavioural assay. Mechanistic insights about protein-ligand interactions were obtained using molecular docking study. Based on the in vitro and in vivo screening data and molecular docking study, a new analogue of GLYX-13, Compound 11a has been found to be as good as the parent compound in all respects.
研究了作为 GLYX-13（一种具有神经保护和抗抑郁特性的临床候选药物）模拟物的应变非常规氨基酸衍生的四肽。分别比较母体 GLYX-13 化合物，对合成的化合物进行了体外和体内的神经突生长和抗抑郁特性筛选。通过神经突长度评估神经突生长特性，通过强迫游泳试验（一种行为测定）中的不动百分比评估抗抑郁特性。使用分子对接研究获得了关于蛋白质 - 配体相互作用的机制见解。根据体外和体内筛选数据以及分子对接研究，已经发现 GLYX-13 的一种新类似物，即化合物 11a，在各方面都与母体化合物一样好。
