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Research focuses on (a) design of gene (RNA)-directed therapeutics based on Antisense, Small interfering RNA (siRNA) and micro-RNA, in which the translation of the RNA specific to a gene is selectively inhibited, (b) Physical and structural chemistry of DNA and RNA foldings,(c) design and synthesis of drug against resistant bacteria. Synthetic organic chemistry of heterocycles and carbohydrates is utilized to design mimics to model biological functions and/or transition state of RNA and DNA.
Akademiska meriter: PhD
Nyckelord: bioorganic chemistry chemical biology rna nucleic acids analogs dna rna interference sirna antisense technology rnase h dnazyme
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Prof Jyoti Chattopadhyaya is a Senior Professor at the Department of Cell & Molecular Biology, University of Uppsala. During his career at Uppsala University he has been working as a Chair of Bioorganic Chemistry as well as Program Director of the Chemical Biology Program at the Department of Cell & Molecular Biology at the University of Uppsala, Sweden. The first program of Bioorganic Chemistry has been established by him in Sweden back in 1980, and since than he has supervised research of 30 Ph.D students, promoted 4 Docents [Dr. Neil Balgobin (1985), Dr. Marek Kwiatkowski (1996), Dr. András Földesi (2004), Dr. Oleksandr Plashkevych (2018)] and has reported high level Bioorganic chemistry research, resulting in over 420 publications in various peer-reviewed Journals (for details see http://www.boc.uu.se). Prof. Chattopadhyaya acknowledges significant contributions to this ground breaking research by his students,co-workers and postdocs whos list (possibly incomplete) is shown below:
Dr. Christelle Dupouy (France, 2007-)
Dr. Liu Yi (China, 2007-)
Dr. Jianfeng Xu (China, 2007-)
Dr. Badgujar Naresh (India, 2007-)
Dr. Andaloussi Mounir (Morocco, 2007)
Dr. Mariappan Mirumari (India, 2005-2006)
Dr. Isaksson Johan (Sweden, 2005)
Dr. Naus Petr (Chez Republic, 2004-2006)
Dr. Bogucka Malgorzata (Poland, 2004-2006)
Dr. Plashkevych Oleksandr (Ukraina, 2000)
Dr. Acharaya Parag (India, 2004)
Dr. Amirkhanov Nariman (Russia, 2003)
Dr. Kumar Pradeep (India, 2005)
Dr. Földesi Andras (Hungary, 2003)
Dr. Ossipov Dimitri ( Russia, 2002)
Dr. Zamaratski Edouard (Russia, 2000)
Dr. Maltseva Tatiana (Russia, 2000)
Dr. Nitin Puri (India, 1999)
Dr. Thibaudeau Christophe (France, 1999)
Dr. Agback Peter (Sweden, 1998)
Dr. Dr. Wen Pei (China, 1998)
Dr. Densov Alexei (Russia, 1998)
Dr. Maini Mitu (India, 1998)
Dr. Guibin Ma (China, 1997)
Dr. Dubey Krishna (India, 1997)
Dr. Hossain Nafizal (India, 1997)
Dr. Kumar Anil (India, 1997)
Dr. Luyten Ingrid (Sweden, 1996)
Dr. Yamakag Schunichi (Japan, 1996)
Dr. Forgó Péter (Hungary, 1995)
Dr. Kolupaev Sergei (Russia, 1995)
Dr. Plavec Janez (Slovenia, 1995)
Dr. Sandström Corine (France, 1995)
Dr. Vasiliev Andrei (Russia, 1995)
Dr. Zhen Xi (China, 1994)
Dr. Nilson Frans Peder (Sweden 1994)
Dr. Paptchikhine Alexander (Russia, 1994)
Dr. Rong Jianhui (China, 1994)
Dr. Rousse Bertrand (France, 1993)
Dr. Sandström Anders (Sweden, 1993)
Dr. Sund Christian (Finland, 1993)
Dr. Tong Weimin (China, 1993)
Dr. Garg Neeraj (India, 1993)
Dr. Poselt Peter (Australia, 1993)
Dr. Viswanadham Garimella (India, 1992)
Dr. Hovinen Jari (Finland, 1992)
Dr. Koole Leo (The Netherlands, 1991)
Dr. Nyilas Agnes (Hungary, 1991)
Dr. Besidsky Yevgeny (Russia, 1991)
Dr. Fedorov Ivan (Russia, 1991)
Dr. Forfar Isabelle (Sweden, 1991)
Dr. Gebru Tesfai (Ethiopia, 1991)
Dr. Wu Jinchang (China, 1990)
Dr. Jaseja Mahesh (India, 1989)
Dr. Katjiteo Ehry (South Africa, 1989)
Dr. Vial Jean-Marc (France, 1989)
Dr. Xiaoguang Luo (China, 1988)
Dr. Zhou Xiaoxiong (China, 1988)
Dr. Bazin Hervé, (France, 1988)
Dr. Pathak Tanmaya (India, 1988)
Dr. Bekiroglu Somer (Turkey, 1987)
Dr. Welch Christopher (UK, 1986)
Dr. Heikkilä Jarmo (Finland, 1985)
Dr. Juntunen Seppo (Finland, 1985)
Dr. Remauld Gerald (France, 1985)
Dr. Gioelli Carlo (Italy, 1984)
Dr. Grouiller Annie (France, 1984)
Dr. Kwiatkowski Marek (Hungary, 1984)
Dr. Sundström Birgitta (Sweden, 1982)
Dr. Balgobin Neil (UK, 1982)
Dr. Bhattacharya Birenda (India, 1982)
Dr. Björkman Sven (Sweden, 1982)
Dr Staffan Josephsson (Sweden) 1979-1982
Dr. Catherine Petit (France, 2002-2004)
Dr. Mrinal Kundu (India, 1998-9)
Former Ph.D. students:
Conformationally Constrained Oligonucleotides for RNA Targeting . Li Qing ISSN 1651-6214; 948 http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-179069 ISBN: 978-91-554-8414-9
Conformationally Constrained Nucleic Acids as Potential RNA Targeting Therapeutics. Zhou Chuanzheng. ISSN 1651-6214; ISBN 978-91-554-7728-8; urn:nbn:se:uu:diva-114136
Conformationally Constrained Nucleosides, Nucleotides, and Oligonucleotides. Design, Synthesis and Properties. Dmytro Honcharenko. ISSN 1651-6214; ISBN 978-91-554-7219-1
Some Aspects of Physicochemical Properties of DNA and RNA. Sandipta Acharya. ISSN 1651-6214; ISBN 91-554-6518-8.
Studies on Nucleic Acids - Structure and Dynamics Johan Isaksson. ISSN 1651-6214, ISBN 91-554-6293-6
Chemically Modified Oligonucleotides: Synthesis, Physicochemical and Biochemical Properties of their Duplexes with DNA and RNA P.I. Pradeepkumar. ISSN 1104-232X, ISBN 91-554-5957-9
Studies on the Non-covalent Interactions (Stereoelectronics, Stacking and Hydrogen Bonding) in the Self-assembly of DNA and RNA . Parag Acharya. ISSN 1104-232X, ISBN 91-554-5821-1
Aspects of Antisense and Antigene of Oligonucleotides Tethered to Intercallators. Dimitri Ossipov. ISBN 91-554-5365-1
Some Aspects of Nucleic Acid Chemistry. Edouard Zamaratski. ISSN 1104-232X, ISBN 91-554-4868-2
Stereoelectronic Effects in Nucleosides and Nucleotides. Christophe Thibaudeau. ISBN 91-554-4365-6
Studies on Nucleic Acids Chemistry. Nitin Puri. ISBN 91-554-4348-6
Synthetic and Structural (NMR) Studies on DNA and RNA. Shun-Ichi Yamakage. ISBN 91-554-3821-0
Studies on Stereoelectronic Effects in Nucleosides and Nucleotides. Janez Plavec. ISBN 91-554-3553-X
Some Recent Developments in Nucleoside Chemistry. Nafizal Hossain. ISBN 91-554-3346-4
Some New Aspects of Nucleoside Chemistry. Zhen Xi. ISBN 91-554-3292-1
Conformational Analysis of Ribonucleic acids (RNA) by NMR Spectroscopy. Peter Agback. ISBN 91-554-3127-5
Studies on Nucleic Acid Chemistry. Andras Földesi. ISBN 91-554-3075-9
Studies on Nucleoside Chemistry. Weimin Tong. ISBN 91-554-3048-1
Studies on Ribonucleic Acid (RNA) Chemistry. Christian Sund. ISBN 91-554-2984-X
Structural Studies on Nucleosides and Nucleotides by Nuclear Magnetic Resonance (NMR) Spectroscopy. Corine Glemarec. ISBN 91-554-2803-7
Studies on Nucleoside Chemistry. Jin-Chang Wu. ISBN 91-554 -2655-7
Synthesis, Separation, and Structure of Ribonucleic Acids and a Toxic Cyclic Peptide. Anders Sandström. ISBN 91-554-2476-7
Studies on Nucleoside and Nucleotide Chemistry. Jean-Marc Vial. ISBN 91-554-2450-3
Studies on Nucleic Acid Chemistry. Xiao-Xiong Zhou. ISBN 91-554-2291-8
Studies on Nucleoside and Nucleotide Chemistry. Tanmaya Pathak. ISBN 91-554-2288-8
Studies on Nucleoside and Nucleotide Chemistry. Agnes Nyilas. ISBN 91-554-2263-2
Studies on Nucleoside Chemistry. Herve Bazin. ISBN 91-554-2073-7
Studies on Nucleoside and Nucleotide Chemistry. Christopher John Welch. ISBN 91-554-1902-X
Studies on the Chemistry of Nucleosides and Nucleotides. Jarmo Heikkilä. ISBN 91-554-1736-1
Studies on Oligoribonucleotide (RNA) Chemistry. Marek Kwiatkowski. ISBN 91-554-1499-0
Studies on Oligodeoxyribonucleotide (DNA) Chemistry. Neil Balgobin. ISBN 91-7146-230-9
Prof. Chattopadhyaya is leading multidisciplinary research at the interface of the frontiers of Chemistry/Structure/Enzymology. His research focuses on (a) design of gene (RNA)-directed therapeutics based on Antisense, Small interfering RNA (siRNA) and micro-RNA, in which the translation of the RNA specific to a gene is selectively inhibited, (b) Physical and structural chemistry of DNA and RNA foldings, (c) design and synthesis of drug against resistant bacteria including hospital infections – MDR and XDR Tuberculosis, Staphylococcus aureus (both methicillin and penicillin resistant), vancomycin resitant Enterococcus and pseudomonas. In these research he employs synthetic organic chemistry of heterocycles and carbohydrates to design mimics to model biological functions and/or the transition state. The major achievements include (a) successful design of new conformationally locked chemically modified nucleo(s)tides, to self-organize oligo-DNA and –RNA molecules to minimize the contribution of entropic energy penalty to the free-energy, (b) to improve the stability and cellular delivery of siRNAs and antisense oligonucleotides; (c) development of new synthetic methodologies for RNA, DNA, and their modified analogs as potential DNA/RNA-directed therapeutics (siRNAs, antisense, triplexing agent, aptamers, etc), including synthetic and physico-chemical aspects of monosaccharide, heterocyclic, and phospholipid, phosphorylating and protecting group chemistry. (d) development of novel active antibiotic lead compounds against multiple drug resistant and extensive drug resistant strains of tuberculosis and hospital pathogens; (e) determination of NMR solution structures of RNA to understand RNA folding-dependent function of non-coding RNAs with emphasis on the role of microRNA, siRNAs and RNA catalyst; (e) elucidation of bioorganic chemical mechanisms using synthetic physical and structural (NMR) chemistry to model transition state or the intermediate of biochemical reactions, such as splicing, RNA catalysis, and RNA-RNA-ligand or RNA-DNA-ligand interactions; (f) development of new chemical tools for RNA, carbohydrate and peptide synthesis to understand molecular details of how structure of molecules dictate function.
Some key references to his work (for details see www.boc.uu.se):
S. Dutta, N. Bhaduri, N. Rastogi, S. G. Chandel, J. Vandavasi, R. S. Upadhayaya, and J. Chattopadhyaya. The carba-LNA modified siRNAs targeting HIV-1 TAR region downregulates HIV-1 replication successfully with Enhanced Potency. MedChemComm, Hot article, 2, 206-216 (2011) http://blogs.rsc.org/md/
C. Zhou, O. Plashkevych, J. Chattopadhyaya. Double Sugar and Phosphate Backbone-constrained Nucleotides: Synthesis, Structure, Stability and Their Incorporation into Oligodeoxynucleotides. Journal of Organic Chemistry, Featured article; 74 (9), 3248–3265 (2009); http://pubs.acs.org/galleyproof/AP-ufiZFcydQcUwd8JbtJ5w
P. Srivastava, J. Barman, W. Pathmasiri, O. Plashkevych, M. Wenska and J. Chattopadhyaya The Five- and Six-Membered Conformationally Locked 2',4'-Carbocyclic ribo-Thymidine: Synthesis, Structure and Biochemical Studies. Journal of the American Chemical Society, 129 (26), 8362 – 8379 (2007).
O. P. Varghese, J. Barman, W. Pathmasiri, O. Plashkevych, D. Honcharenko, and J. Chattopadhyaya Conformationally Constrained 2'-N,4'-C-Ethylene-Bridged Thymidine (Aza-ENA-T): Synthesis, Structure, Physical, and Biochemical Studies of Aza-ENA-T-Modified Oligonucleotides. Journal of the American Chemical Society, 128 (47), 15173–15187 (2006).
Currently active particularly successful research areas and groups/networks, in a national or international perspective led by Prof. Chattopadhyaya
● Strong and fruitful collaboration with the infectious diseases, chemical biology and systems biology groups involved in Linnéa sponsored RNA research Consortium concentrating on “Design and Synthesis of Site-specific Bifunctional Ligands Targeted to RNA hairpin loops depending upon their Stem-Loop-size and Sequence-context” funded by the Swedish Research Council (Natural and Technical Research), “Strategic Funding of Uppsala RNA Research Center (URRC) (VR diary No 349-2006-267). Within this project we design and synthesis unique specific Ruthenium based organometalic compounds as well as metallopeptides that are aimed to bind to the sequence-specific stem-loop motif of pre-micro-RNA structure with a far reaching aim to modulate the biosynthesis, and consequently regulating the cellular function of micro-RNA.
● RNA research which is holding very high international level as recognized by the referees of 2010 VR application (VR diary No 2010-4991). This research is focused on three main goals: 1) specific RNA- and chemically modified RNA- synthesis, 2) structure and conformational determination of RNA and 3) studies of RNA function.
● Prof. Chattopadhyaya has been nominated as a Research Professor by the Dept of Science & Technology, India Gov since 2009. In that capacity, he helps to organize strategic research on biotechnology of CSIR/India in an international perspective.
● Prof. Chattopadhyaya is an honorary professor at Jilin University in China, and nominated honorary professor at Nankai University in China.
● Prof.Chattopadhyaya collaborates and actively helped to organize research with 26 scientists at the Institute of Molecular Medicine at Pune/India to devise therapeutics against resistant infectious diseases.
● He has conceived and demonstrated the concept of Stereoelectronic effects in DNA and RNA and their structural and functional implications, which has found wide applications and acceptance internationally (http://www.boc.uu.se/boc14www/publications/Stereoelectronic_effect.pdf ).
● He has conceived and demonstrated the concept of The Uppsala NMR-window concept to simplify the NMR spectra of large DNA/RNA, which is used worldwide.
● He has conceived and demonstrated the design principles for the synthesis of new conformationally-constrained nucleic acids and their enzymology to develop effective antisense oligos and siRNAs to enhance blood serum stability and facilitate delivery.
● He has conceived and demonstrated the design principles for the Synthesis and modifications of aza-modified conformationally restricted nucleotides as fluorescent DNA probes.
● He has conceived and demonstrated that the single-strand DNA and RNA conformation in the purine-rich single-strand oligo-DNA and –RNA are well pre-organized to helical form - not random coils as it was originally thought. The structure of the self-assembled single-strand oligo-DNA and -RNA is very much reminiscent of their double-stranded counterparts. The set of papers published from Uppsala on self-assembled single-strand oligo-DNA and -RNA has brought about a paradigm shift after Watson-Crick basepaired double helix as the origin of helical structure of DNA duplex
● He and his coworkers have shown that all internucleotidic phosphodiester bonds in RNA are not chemically equivalent, and their reactivity depends upon the sequence-context governed by specific intrinsic electrostatic interactions.
● He and his coworkers have developed solid-phase oligo-RNA synthesis utilizing our new 2'-O-TEM protecting group.
● He and his cowrkers have designed, synthesized, performed biological evaluation and molecular modeling studies of novel quinoline, triazole, urea and thiourea derivatives against drug resistant Mycobacterium tuberculosis.
List of present grants (exchange rate €1 = 9.41725 SEK)
- EU FP 6th, “RIGHT, RNA Interference Technology as Human Therapeutic Tool” 2005, 2006, 2007, 2008 : 200,000 €/year UU project number: 15250900, EU RIGHT contract number: 005276
- Swedish Research Council (Medical Research), “New Nucleolitically Stable Antisense Oligonucleotides Which Recruits RNase H and cleave target RNA” 2008, 2009, 2010. 85,000 €/year (ID number: 521-2007-2400) UU project number: 15250806, VR Contract ID K2008-66X-14224-07-3
- Swedish Research Council (Natural and Technical Research VR) ”Synthesis, Structure and Function of RNA” 2008, 2009, 2010. 117,000 €/year (ID number: 621-2007-4466), UU project number: 15250807, VR Contract ID 70446601
- Swedish Research Council (Natural and Technical Research VR) ” Synthesis, Structure and Function of RNA” 2008 53,000 € /year (ID number: 621-2007-4466) UU project number: 15250808, VR Contract ID: 70446602
- Swedish Research Council (Natural and Technical Research VR “Strategic Funding of Uppsala RNA Research Center (Urrc) 70,000 €/year 2006-07-01, 2008, 2009,2010 (ID number 349-2006-267) UU project number 15250805, VR contract ID: 60026701
- EU FP7, “NATT” (New Approaches to target Tuberculosis) 2008, 2009, 2010 ( tot €402000) 117,000 €/year
- Swedish Research Council (Natural and Technical Research VR) ”Synthesis, Structure and Function of RNA” 2011, 2012, 2013: 117,000 €/year (ID number: 621-2011-4466)
- Swedish Research Council (Medical Research), “New Nucleolitically Stable Antisense Oligonucleotides Which Recruits RNase H and cleave target RNA” 2011, 2012, 2013, 2014: 85,000 €/year (ID number: 521-2011-2400)
- Swedish Research Council (Natural and Technical Research VR “Strategic Funding of Uppsala RNA Research Center (Urrc) 70,000 €/year 2011, 2012 (ID number 349-2006-267)
- Swedish Research Council, Grant for organizing conference “Development of drugs against resistant forms of tuberculosis and other infectious diseases" at the Biomedical Center, Uppsala University. 9600 €, 2011
The complete list of 420 publications can be found following the link:
ISI Web of knowledge Citation Report: Results found: 350; Sum of the Times Cited: 6111; Sum of Times Cited without self-citations: 4243; Average Citations per item: 17.46; H-index: 36
Highlights of 30-Years of Bioogranic Chemistry research at Uppsala University can be found following the link: http://www.boc.uu.se/boc14www/publications/survey_isbn.pdf
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