scholarly journals Combination of 2D/3D Ligand-Based Similarity Search in Rapid Virtual Screening from Multimillion Compound Repositories. Selection and Biological Evaluation of Potential PDE4 and PDE5 Inhibitors

Molecules ◽  
2014 ◽  
Vol 19 (6) ◽  
pp. 7008-7039 ◽  
Author(s):  
Krisztina Dobi ◽  
István Hajdú ◽  
Beáta Flachner ◽  
Gabriella Fabó ◽  
Mária Szaszkó ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Similarity Search ◽  
Biological Evaluation ◽  
Pde5 Inhibitors

scholarly journals Structure-Based Virtual Screening and Biological Evaluation of Peptide Inhibitors for Polo-Box Domain

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 107 ◽  
Author(s):  
Fang Yan ◽  
Guangmei Liu ◽  
Tingting Chen ◽  
Xiaochen Fu ◽  
Miao-Miao Niu
Keyword(s):  
Cell Cycle ◽  
Virtual Screening ◽  
Fold Increase ◽  
Pharmacophore Modeling ◽  
Biological Evaluation ◽  
Peptide Inhibitors ◽  
Regulatory Proteins ◽  
Competitive Binding Assay ◽  
M Phase ◽  
Cell Cycle Regulatory Proteins

The polo-box domain of polo-like kinase 1 (PLK1-PBD) is proved to have crucial roles in cell proliferation. Designing PLK1-PBD inhibitors is challenging due to their poor cellular penetration. In this study, we applied a virtual screening workflow based on a combination of structure-based pharmacophore modeling with molecular docking screening techniques, so as to discover potent PLK1-PBD peptide inhibitors. The resulting 9 virtual screening peptides showed affinities for PLK1-PBD in a competitive binding assay. In particular, peptide 5 exhibited an approximately 100-fold increase in inhibitory activity (IC50 = 70 nM), as compared with the control poloboxtide. Moreover, cell cycle experiments indicated that peptide 5 effectively inhibited the expression of p-Cdc25C and cell cycle regulatory proteins by affecting the function of PLK1-PBD, thereby inducing mitotic arrest at the G2/M phase. Overall, peptide 5 can serve as a potent lead for further investigation as PLK1-PBD inhibitors.

Peptide Similarity Search Based and Virtual Screening Based Strategies to Identify Small Molecules to Inhibit CarD–RNAP Interaction in M. tuberculosis

2018 ◽  
Vol 25 (2) ◽  
pp. 697-709 ◽  
Author(s):  
V. G. Shanmuga Priya ◽  
Priya Swaminathan ◽  
Uday M. Muddapur ◽  
Prayagraj M. Fandilolu ◽  
Rishikesh S. Parulekar ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Small Molecules ◽  
Similarity Search
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