کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6369099 | 1623804 | 2016 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
In silico approaches to identify the potential inhibitors of glutamate carboxypeptidase II (GCPII) for neuroprotection
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم کشاورزی و بیولوژیک
علوم کشاورزی و بیولوژیک (عمومی)
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: In silico approaches to identify the potential inhibitors of glutamate carboxypeptidase II (GCPII) for neuroprotection In silico approaches to identify the potential inhibitors of glutamate carboxypeptidase II (GCPII) for neuroprotection](/preview/png/6369099.png)
چکیده انگلیسی
To develop a potential inhibitor for glutamate carboxypeptidase II (GCPII) effective against all the eight common genetic variants reported, PyMOL molecular visualization system was used to generate models of variants using the crystal structure of GCPII i.e. 2OOT as a template. High-throughput virtual screening of 29 compounds revealed differential efficacy across the eight genetic variants (pIC50: 4.70 to 10.22). Pharmacophore analysis and quantitative structure-activity relationship (QSAR) studies revealed a urea-based N-acetyl aspartyl glutamate (NAAG) analogue as more potent inhibitor, which was effective across all the genetic variants of GCPII as evidenced by glide scores (â4.32 to â7.08) and protein-ligand interaction plots (13 interactions in wild GCPII). This molecule satisfied Lipinski rule of five and rule of three for drug-likeliness. Being a NAAG-analogue, this molecule might confer neuroprotection by inhibiting glutamatergic neurotransmission mediated by N-acetylated alpha-linked acidic dipeptidase (NAALADase), a splice variant of GCPII.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Theoretical Biology - Volume 406, 7 October 2016, Pages 137-142
Journal: Journal of Theoretical Biology - Volume 406, 7 October 2016, Pages 137-142
نویسندگان
Shaik Mohammad Naushad, M. Janaki Ramaiah, Balraj Alex Stanley, S. Prasanna Lakshmi, J. Vishnu Priya, Tajamul Hussain, Salman A. Alrokayan, Vijay Kumar Kutala,