当前位置: X-MOL 学术Curr. Comput.-Aided Drug Des. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Nitric Oxide Inhibition Assay and the Respective Target Identification of an Aptamer Designed to Control Atherosclerosis.
Current Computer-Aided Drug Design ( IF 1.5 ) Pub Date : 2021-01-01 , DOI: 10.2174/1573409917666210203092946
Anant Achary 1 , Subramanian Manibalan 1 , Pilavadiyan Akshaysri 1 , Sethuraman Thabusree 1 , Madasamy Chitra 1 , Mani Vasanthi 1
Affiliation  

INTRODUCTION Aptamers are emerging newer therapeutics and diagnostics whichcan be designed to bind any kind of target proteins. Vascular endothelial damage by the excess amount of nitric oxide production in systemic circulation leads to the secretion of inflammatory chemoattractants and cell adhesions are the prime pro-atherogenic events in the formation of plagues at atrial intimal layers due to oxidation - sensitive mechanisms. Nitric oxide inhibition assay is one of the valuable qualitative anti-atherosclerosis matrices. METHODS In this research, Nitric oxide inhibition efficiency of an ssDNA aptamer on cell lines was studied, and the respective targets of that aptamer were identified by network analysis. The aptamer used here was originally designed for Selectin P Ligand Protein to control the atherogenic process. 20 nM of aptamer solution in LipofectamineTM 2000 sshowshighest level 70.5% inhibition of nitric oxide liberation on 24 hours cultured medium of lipopolysaccharide stimulated murine macrophage RAW 264.7 cell lines. RESULTS Protein interaction network analysis of the nitric oxide synthesis pathway interactors and the molecular docking analysis with network resulted in proteins such as AKT serine/threonine kinase 1, calmodulin, estrogen receptor 1, and nitric oxide synthase-3, which confirmed that the G - quadruplex Model of 18-mer sequence effectively bound to the active sites of estrogen receptor 1, and nitric oxide synthase-3. CONCLUSION The aptamer designed for atherosclerotic target has also exertedsignificant nitric oxide inhibition to control the atherogenic events through the proteins such as, AKT1, NOS3 and ESR1.

中文翻译:

一氧化氮抑制测定和旨在控制动脉粥样硬化的适体的相应靶标鉴定。

引言适体是新兴的新型治疗和诊断方法,可设计用于结合任何类型的靶蛋白。体循环中过量一氧化氮产生引起的血管内皮损伤导致炎症化学引诱物的分泌,细胞粘附是由于氧化敏感机制在心房内膜层形成瘟疫的主要促动脉粥样硬化事件。一氧化氮抑制测定是有价值的定性抗动脉粥样硬化基质之一。方法本研究研究了一种ssDNA适体对细胞系的一氧化氮抑制效率,并通过网络分析确定了该适体的各自靶点。此处使用的适体最初是为选择素 P 配体蛋白设计的,以控制动脉粥样硬化过程。LipofectamineTM 2000 中的 20 nM 适体溶液在脂多糖刺激的鼠巨噬细胞 RAW 264.7 细胞系的 24 小时培养基上显示最高水平 70.5% 的一氧化氮释放抑制。结果一氧化氮合成途径相互作用物的蛋白质相互作用网络分析和与网络的分子对接分析产生了AKT丝氨酸/苏氨酸激酶1、钙调蛋白、雌激素受体1和一氧化氮合酶3等蛋白质,证实了G- 18-mer 序列的四链体模型有效结合雌激素受体 1 和一氧化氮合酶 3 的活性位点。结论针对动脉粥样硬化靶点设计的适配体还通过AKT1、NOS3和ESR1等蛋白对一氧化氮产生显着的抑制作用,从而控制动脉粥样硬化的发生。
更新日期:2021-02-02
down
wechat
bug