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Chiara Luise

M.Sc. Chiara Luise

e-mail: luisechi(at)hotmail.it

Tel.:

Structure-based design and optimization of inhibitors of histone lysine methyltransferases and methyl-lysine reader proteins

In this research project, the focus is on methyl-lysine reader proteins including Spindlin1, Lethal(3) Malignant Brain Tumor-Like protein 3 (L3MBTL3)  and Chromodomain-helicase-DNA-binding protein 1 (CHD1). Given the growing interest of these reader proteins in the field of epigenetic, there is a high need to develop selective inhibitor probes. Indeed, the identification and development of novel chemotypes against these targets represent challenging field of research.

A combination of in silico techniques, synthetic chemistry and in vitro biochemical assays is employed for screening of novel selective inhibitors of these targets. Specifically, the current work is focusing on the computational chemistry part with the aim to investigate potential candidates by applying computer-aided approaches like molecular docking, virtual screening, pharmacophore generation, molecular dynamic simulations and binding free energy calculations. Once identified and optimized, these inhibitors could, on the one hand, be potential therapeutics for several disorders and on the other be utilized as pharmacological tools to further investigate individual reader proteins and characterize their physiological role.

Publications

2021

C. Luise, D. Robaa, W. Sippl. Exploring aromatic cage flexibility of the histone methyllysine reader protein Spindlin1 and its impact on binding mode prediction - an in silico study JCAMD, in press

K.T. Shukur, T. Ercetin, C. Luise, W. Sippl, O. Sirkecioglu, M. Ulgen, G.P. Coskun, M. Yarim, M. Gazi, H.O. Gulcan. Design, synthesis, and biological evaluation of new urolithin amides as multitarget agents against Alzheimer's disease. Arch Pharm (Weinheim). 2021 Jan 29:e2000467. doi:10.1002/ardp.202000467    

2020

D. Robaa, J. Melesina, C.Luise, W. Sippl. Structure-based design of epigenetic inhibitors. In: Chemical Epigenetics   , Springer Nature Switzerland AG. Topics in Medicinal Chemistry, 2020. ISBN 978-3-030-42982-9 (eBook) https://link.springer.com/book/10.1007%2F978-3-030-42982-9   

Noshadi B, Ercetin T, Luise C, Yuksel MY, Sippl W, Sahin MF, Gazi M, Gulcan HO. Synthesis, Characterization, Molecular docking, and Biological Activities of Some Natural and Synthetic Urolithin Analogues. Chem Biodivers. 2020 Jun 4. doi:10.1002/cbdv.202000197--   

2019

N. Miekus, C. Luise, W. Sippl, T. Baczek, C. E.H. Schmelzer, A. Heinz. MMP-14 degrades tropoelastin and elastin. Biochimie.165:32-39, 2019. doi:10.1016/j.biochi.2019.07.001   

2018

C. Luise, D. Robaa. Application of Virtual Screening Approaches for the Identification of Small Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1. Methods Mol Biol. 2018;1824:347-370. doi:10.1007/978-1-4939-8630-9_21   .

A. C. Mora Huertas, C. E. H. Schmelzer, C. Luise, W. Sippl, M. Pietzsch, W. Hoehenwarter, A. Heinz. Degradation of tropoelastin and skin elastin by neprilysin. Biochimie, 146:73-78, 2018.  doi.org/10.1016/j.biochi.2017.11.018

2017

M. Schiedel, A. Fallarero, C. Luise, W. Sippl, P. Vuorela, and M. Jung. Synthesis and biological evaluation of 8-hydroxy-2,7-naphthyridinium salts as potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Med. Chem. Comm. 8, 465-470, 2017. DOI:10.1039/C6MD00647G   

2016

D. Robaa, T. Wagner, C. Luise, L. Carlino, J. McMillan, R. Flaig, R. Schüle, M. Jung, and W. Sippl. Identification and SAR studies of Small-Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1. ChemMedChem.11, 2327-2338, 2016. doi: 10.1002/cmdc.201600362

Posters

C. Luise, D. Robaa, T. Wagner, R. Schüle, M. Jung W. Sippl.
Virtual Screening Based Identification of Novel Small Molecule Inhibitors of the Methyl-Lysine Reader Spindlin1.
EUROPIN Summer School on Drug Design, September 17^th - 22^nd, 2017, Vienna, Austria.
The poster was awarded second place in the poster competition.

C. Luise, D. Robaa, W. Sippl.
Docking and Binding Free Energy Calculations of Ligand Binding to L3MBTL3 Methyl-Lysine Reader Domain.
11^th European Workshop in Drug Design and Mu.Ta.Lig. Training School, May 21^st - 26^th, 2017, Siena, Certosa di Pontignano, Italy.

C. Luise, D. Robaa, W. Sippl.
Binding Free Energy Prediction for Ligand Binding to L3MBTL3 Methyl-Lysine Reader Domain.
3^rd Freiburg Epigenetic Spring Meeting: Chemical Biology of Epigenetics, April 10^th - 13^th, 2016, Freiburg, Germany.

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