Please use this identifier to cite or link to this item:
https://doi.org/10.1002/anie.201609427
Title: | Development of Cell-Permeable, Non-Helical Constrained Peptides to Target a Key Protein–Protein Interaction in Ovarian Cancer | Authors: | Wiedmann, M.M Tan, Y.S Wu, Y Aibara, S Xu, W Sore, H.F Verma, C.S Itzhaki, L Stewart, M Brenton, J.D Spring, D.R |
Keywords: | Chemotherapy Diseases Drug products Molecular dynamics Transcription Transcription factors X ray crystallography Crystallographic data Drug discovery Hepatocyte nuclear factors Molecular dynamics simulations Nuclear import Peptide therapeutics Peptidomimetics Platinum-based chemotherapy Peptides cell penetrating peptide protein binding chemical structure chemistry drug effect female human metabolism molecular dynamics molecular model ovary tumor X ray crystallography Cell-Penetrating Peptides Crystallography, X-Ray Female Humans Models, Molecular Molecular Dynamics Simulation Molecular Structure Ovarian Neoplasms Protein Binding |
Issue Date: | 2017 | Publisher: | Wiley-VCH Verlag | Citation: | Wiedmann, M.M, Tan, Y.S, Wu, Y, Aibara, S, Xu, W, Sore, H.F, Verma, C.S, Itzhaki, L, Stewart, M, Brenton, J.D, Spring, D.R (2017). Development of Cell-Permeable, Non-Helical Constrained Peptides to Target a Key Protein–Protein Interaction in Ovarian Cancer. Angewandte Chemie - International Edition 56 (2) : 524-529. ScholarBank@NUS Repository. https://doi.org/10.1002/anie.201609427 | Rights: | Attribution 4.0 International | Abstract: | There is a lack of current treatment options for ovarian clear cell carcinoma (CCC) and the cancer is often resistant to platinum-based chemotherapy. Hence there is an urgent need for novel therapeutics. The transcription factor hepatocyte nuclear factor 1β (HNF1β) is ubiquitously overexpressed in CCC and is seen as an attractive therapeutic target. This was validated through shRNA-mediated knockdown of the target protein, HNF1β, in five high- and low-HNF1β-expressing CCC lines. To inhibit the protein function, cell-permeable, non-helical constrained proteomimetics to target the HNF1β–importin β protein–protein interaction were designed, guided by X-ray crystallographic data and molecular dynamics simulations. In this way, we developed the first reported series of constrained peptide nuclear import inhibitors. Importantly, this general approach may be extended to other transcription factors. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim | Source Title: | Angewandte Chemie - International Edition | URI: | https://scholarbank.nus.edu.sg/handle/10635/179270 | ISSN: | 1433-7851 | DOI: | 10.1002/anie.201609427 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
Show full item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
10_1002_anie_201609427.pdf | 3.19 MB | Adobe PDF | OPEN | None | View/Download |
This item is licensed under a Creative Commons License