Our research focuses on developing chemical and synthetic biology tools for molecular level understanding of the histone code with implications in fundamental science and drug discovery. My group will develop cyclic peptide-based ligands to modulate specific epigenetic PTM states of histones both in vitro and in vivo. We aim to mimic the epigenetic modifications of histones e.g. methylation, acetylation, ubiquitination using genetic code expansion technique to understand the molecular basis of crosstalks and their roles in controlling the chromatin landscape. We aim to rescue the loss-of-function effect of oncohistone mutations by site specifically introducing specific PTM by genetic code expansion. We want to incorporate photocrosslinker AA in histones to study PTM readers and erasers.
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Cyclic peptides made from synthetic and genetically encoded fragments by Palei S., Mootz H. D. ChemBioChem 17 378-382 (2016)
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A high-throughput effector screen identifies a novel small molecule scaffold for inhibition of ten-eleven translocation dioxygenase by Palei* S., Weisner* J. , Vogt M. , Gontala R. , Buchmuller B. , Ehrt C. , Grabe T. , Kleinbölting S. , Müller M. , Clever G. , Rauh D. , Summerer D. RSC Med. Chem. 13 1540-1548 (2022)
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Preparation of semisynthetic macrocycle using split inteins by Palei S., Mootz H. D. Methods in Molecular Biology 77-92 (2017)
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Bacterial cell surface display of semisynthetic cyclic peptide by Palei* S., Becher* K. , Nienberg C. , Jose J. , Mootz H. D. ChemBioChem 20 72-77 (2019)
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Light-Activatable TET-Dioxygenases Reveal Dynamics of 5-Methylcytosine Oxidation and Transcriptome Reorganization by Palei S., Buchmuller B. , Wolffgramm J. , Muñoz-lopez Á. , Jung S. , Czodrowski P. , Summerer D. J. Am. Chem. Soc. 142 7289-7294 (2020)
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Semisynthetic head-to-tail cyclized peptides obtained by combining protein trans-splicing and intramolecular expressed protein ligation by Palei S., Mootz H. D. Chem. Commun. 57 4194-4197 (2021)
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Light-Control of DNA-Methyltransferase Catalysis for Time-Resolved In Vivo Chromatin Studies by Wolffgramm J., Buchmuller B. , Palei S. , Munoz-lopez A. , Kane J. , Janning P. , Schweiger M. , Summerer D. Angew. Chem. Int. Ed. 60 13507-13512 (2021)
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Evolved DNA Duplex Readers for Strand-Asymmetrically Modified 5-Hydroxymethylcytosine/5-Methylcytosine CpG Dya by Buchmuller B., Dröden J. , Singh H. , Palei S. , Drescher M. , Linser R. , Summerer D. J. Am. Chem. Soc. 144 2987-2993 (2022)
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Optochemical Studies Enable Kinetic Insights into the Domain-Dependent Interplay of TET1 and MBD1 while Reading and Oxidizing 5-Methylcytosine by Lin T., Palei S. , Summerer D. ACS Chem. Bio. 17 1844-1852 (2022)
Principal Investigator
- A phage display platform for discovery of semisynthetic cyclic peptide inhibitors of readers, writers and erasers of histone post-translational modifications. Sponsored Research and Industrial Consultancy (SRIC)
- A ribosomal display platform for directed evolution of semisynthetic cyclic peptide inhibitors of readers, writers and erasers of histone post-translational modifications. Anusandhan National Research Foundation (ANRF)
- Developing chemical biology and therapeutics toolbox to understand the molecular basis of the histone code DEPARTMENT OF BIOTECHNOLOGY
- Directed Evolution of Enzyme in the Crowded Confinement of DNA Synthetic Cells DBT, NEW DELHI
Co-Principal Investigator
- Engineering allosteric regulation in an intein enzyme and its application for the synthesis and purification of linear and cyclic therapeutic peptides from bacteria DBT, NEW DELHI
Ph. D. Students
Arun Biswas
Area of Research: Synthetic Biology for Targeted Delivery
Nandini Dutta
Area of Research: Ribosomal display of cyclic peptides
Pratyusha Adak
Area of Research: Directed evolution of intein enzyme
Sonia Baidya
Area of Research: Phage display of cyclic peptides
Souvik Sasmal
Area of Research: Chemical Biology