Staff scientist

Location:

Rockville, MD

Posted:

April 22, 2012

Contact this candidate

Resume:

Dilip K. Tosh, PhD

Molecular Recognition Section, Laboratory of Bioorganic Chemistry,

National Institute of Diabetes and Digestive and Kidney Diseases,

National Institute of Health, Bethesda, Maryland 20892 USA

Email: vcgt98@r.postjobfree.com

Phone: 1-240-***-**** (Mobile)

RESEARCH EXPERIENCE

2008–present Research Fellow

Molecular Recognition Section, Laboratory of Bioorganic Chemistry,

National Institute of Diabetes and Digestive and Kidney Diseases,

National Institute of Health, Bethesda

Mentor: Dr. Kenneth A. Jacobson

• Designed and synthesized various nucleosides and hetercyclic ligands for adenosine receptors; targeting for cardiac protection, anticonvulsant agent for epilepsy seizure suppression, cancer, muscle protection and eye diseases.

• Developed multivalent dendrimer conjugated ligands for adenosine receptors and P2Y receptors.

2005-2008 Post Doctoral Fellow

Laboratory of Medicinal Chemistry, College of Pharmacy,

Ewha Womans University, Seoul, Republic of Korea

Mentor: Prof. Lak Shin Jeong

• Developed for the first time a novel method for synthesis of seleno nucleosides, a new generation of nucleosides having anti-cancer, anti-tumor and anti-viral activities.

• Developed new methods for synthesis of carba nucleosides, thio nucleosides, locked nucleosides and oxa nucleosides for anti-viral and anti-cancer research.

1999-2005 Graduate Assistant, Indian Institute of Technology, Bombay, India

Advisor: Prof. V. K. Singh

• Completed formal total synthesis hirsutic acid and complicatic acid by ten steps which is the best method so far reported in literature.

• Developed a new method for synthesis of AB ring system of taxane.

1997-1999 Post MS project, Department of Chemistry, Berhampur University,

Berhampur, India.

• Developed a general method for synthesizing various 1-amino-2-arylimidazolin-5-ones and studied their various chemical reactions.

RESEARCH INTEREST:

Drug discovery, medicinal chemistry, chemical biology, organic synthesis, nucleoside chemistry, adenosine recepetors, P2Y receptors, anti-viral, nanotechnology.

EDUCATION

• PhD, Synthetic Organic Chemistry,

Indian Institute of Technology, Bombay, India, 2005

Thesis Title: “Studies on synthesis of hirsutic acid and AB ring system of taxane”

• MS, Chemistry, Utkal University, Bhubaneswar, India, 1997

• BS, Chemistry, Utkal University, Bhubaneswar, India, 1995

PROFESSIONAL EXPERIENCES

• Extensive experience in medicinal chemistry, synthetic chemistry, drug discovery and development.

• Broad experience in nucleoside and nucleotide chemistry, carbocyclic chemistry and heterocyclic chemistry.

• Extensive experience in development of new templates for adenosine receptors, P2Y receptors and anti-viral research.

• Extensive track record of designing bioactive molecules and moving those compounds to development pipeline

• Strong collaborative experiences with pharmacologist, molecular biologists, clinicians and computational chemists.

• Experienced in developing various dendrimer conjugated ligands.

• Strong background in multi step synthesis and characterization of new molecules.

• Extensive experience in mentoring students and junior scientists.

ACADEMIC/PROFESSIONAL HONORS

• Editorial Board member of the journal “Dataset Papers in Pharmacology” Hindawi Publishing Corporation.

• 2008-till present, NIH Fellowship, by National Institute of Health.

• 2001-2004, Senior Research Fellowship by Council of Scientific and Industrial Research (CSIR), New Delhi, India.

• 1999-2001, Junior Research Fellowship by Council of Scientific and Industrial Research (CSIR), New Delhi, India.

• 1999, Qualified on the National Eligibility Test (NET) conducted by Council of Scientific and Industrial Research (CSIR) and University Grant Commission (UGC) of India.

• 1999, Qualified Graduate Aptitude Test in Engineering (GATE), India.

• Laboratory expert in 33rd International Chemistry Olympiad, 2001.

• Member of American Chemical Society and Indian Chemical Society.

PATENTS

• Jacobson, K. A.; Tosh, D. K. “Preparation of methanocarba adenosine derivatives and PAMAM dendrimer thereof as agonist/antagonist conjugates PCT Int. Appl. (2011), WO 201******* A1 20110609.

• Jacobson, K. A.; Tosh, D. K. “A3 Adenosine receptor agonists and antagonists” US Patent Application No 13/371,081 (HHS Reference: E-140-2008/1-US-01).

PEER REVIEWED PUBLICATIONS

1. Tosh, D. K.; Deflorian, F.; Phan, K.; Gao, Z.-G.; Wan, T. C.; Gizewski, E.; Auchampach, J. A.; Jacobson, K. A. “Structure-Guided Design of A3 Adenosine Receptor-Selective Nucleosides: Combination of 2-Arylethynyl and Bicyclo[3.1.0]hexane Substitutions” Journal of Medicinal Chemistry 2012, 55, 000 (in press).

2. Tosh, D. K.; Phan, K.; Gao, Z.-G.; Gakh, A. A.; Xu, F.; Deflorian, F.; Abagyan, R.; Stevens, R. C.; Jacobson, K. A.; Katritch, V. “Optimization of adenosine 5 -carboxamide derivatives as adenosine receptor agonists using structure-based ligand design and fragment-based searching” Journal of Medicinal Chemistry 2012, 55, 000 (in press).

3. Tosh, D. K.; Phan, K. Deflorian, F.; Wei, Q.; Yoo, L. S.; Gao, Z.-G.; Jacobson, K. A. “Click Modification in the N6 Region of A3 Adenosine Receptor-Selective Carbocyclic Nucleosides for Dendrimeric Tethering that Preserves Pharmacophore Recognition” Bioconjugate Chemistry 2012, 23, 232-247.

4. Chen, Z.; Janes, K.; Chen, C.; Doyle, T.; Bryant, L.; Tosh, D. K.; Jacobson, K. A.; Salvemini; D. “Controlling murine and rat chronic pain through A3 adenosine receptor activation” The FASEB, 2012, 000.

5. Chanyshev, B.; Shainberg, A.; Isak, A.; Litinsky, A.; Chepurko, Y.; Tosh, D. K.; Phan, K; Gao, Z.-G.; Hochhauser, E.; Jacobson, K. A. “Anti-ischemic effects of multivalent dendrimeric A3 adenosine receptor agonists in cultured cardiomyocytes and in the isolated rat heart” Pharmacological Research, 2012, 65, 338-346.

6. Wan, T. C.; Tosh, D. K.; Du, L.; Gizewski, E. T.; Jacobson, K. A.; Auchampach, J. A. “Polyamidoamine (PAMAM) dendrimer conjugate specifically activates the A3 adenosine receptor to improve post-ischemic/reperfusion function in isolated mouse hearts” BMC Pharmacology, 2011, 11, 11.

7. Tosh, D. K.; Phan, K. Deflorian, F.; Wei, Q.; Gao, Z.-G.; Jacobson, K. A. “Truncated (N)-Methanocarba Nucleosides as A1 Adenosine Receptor Agonists and Partial Agonists: Overcoming Lack of a Recognition Element” ACS Medicinal Chemistry Letter 2011, 2, 626-631.

8. Kecskés, A.; Tosh, D. K.; Wei, Q.; Gao, Z.-G.; Jacobson, K. A. “A. GPCR Ligand Dendrimer (GLiDe) Conjugates: Adenosine Receptor Interactions of a Series of Multivalent Xanthine Antagonists” Bioconjugate Chemistry 2011, 22, 1115-1127. ( Authors contributed equally to this paper).

9. Tosh, D. K.; Yoo, L. S.; Chinn, M.; Hong, K.; Kilbey II, S. M.; Barrett, M. O.; Fricks, I. P.; Harden, T. K.; Gao, Z.-G.; Jacobson, K. A. “Polyamidoamine (PAMAM) Dendrimer Conjugates of “Clickable” Agonists of the A3 Adenosine Receptor and Coactivation of the P2Y14 Receptor by a Tethered Nucleotide” Bioconjugate Chemistry 2010, 21, 372-384.

10. Tosh, D. K.; Chinn, M.; Yoo, L.; Kang, D. W.; Luecke, H.; Gao, Z. G.; Jacobson, K. A. “2-Dialkynyl Derivatives of (N)-Methanocarba Nucleosides: Clickable A3 Adenosine Receptor-Selective Agonists” Bioorganic Medicinal Chemistry 2010, 18, 508-517.

11. Maruoka, H.; Ko, H.; Barrett, M. O.; Tosh, D. K.; Fricks, I.; Melman, A.; Carter, R.; Burianek, L. B.; Berk, B.; Costanzi, S.; Harden, T. K.; Jacobson, K. A. “ Structure Activity Relationship of UDP Analogues as P2Y6 Receptor Agonists: Novel (S)-Methanocarba Ribonucleotides and 5'-Triphospate γ-Ester Derivatives” Journal of Medicinal Chemistry 2010, 53, 4488-4501.

12. Alexander, V.; Choi, W. J.; Chun, J.; Kim, H. O.; Jeon, J. H.; Tosh, D. K.; Lee, H. W.; Chandra, G.; Choi, J.; Jeong, L. S. “A New DNA Building Block, 4 -Selenothymidine: Synthesis and Modification to 4 -Seleno-AZT as a Potential Anti-HIV Agent” Organic Letters 2010, 12, 2242-2245.

13. Tosh, D. K.; Chinn, M; Ivanov, A. A; Klutz, A. M.; Gao, Z. G. “Functionalized Congeners of A3 Adenosine Receptor-Selective Nucleosides Containing a Bicyclo[3.1.0]hexane Ring System” Journal of Medicinal Chemistry 2009, 52, 7580-7592.

14. Jeong, L. S.; Tosh, D. K.; Choi, W. J.; Lee, S. K.; Kang, Y.-J.; Choi, S.; Lee, J. H.; Lee, H.; Lee, H. W.; Kim, H. O. “ Discovery of a New Template for Anticancer Agents: 2 -deoxy-2 -fluoro-4 -selenoarabinofuranosylcytosine (2 -F-4 -Seleno-ara-C)” Journal of Medicinal Chemistry 2009, 52, 5303-5306.

15. Tosh, D. K.;* Jacobson, K. A.; Jeong; L. S. “Nucleoside-Based A3 Adenosine Receptor Antagonist as Drug Candidates” Drugs of the Future 2009, 34, 43-52.

(* Corresponding author)

16. Jeong, L. S.; Tosh, D. K., Choi, W. J. “Development of next generation 4 - Selenonucleosides” Nucleic Acids Symposium Series 2009, 53, 7-8.

17. Tosh, D. K.; Choi, W. J.; Kim, H. O.; Lee, Y.; Pal, S.; Hou, X.; Choi, J.; Choi, S.; Jeong, L. S. “ Stereoselective Synthesis and Conformational Study of Novel 2 , 3 -Didehydro-2 ,3 -dideoxy-4 -selenonucleosides” Journal of Organic Chemistry 2008, 73, 4259-4262.

18. Jeong, L. S.; Tosh, D. K.; Kim, H. O.; Wang, T.; Hou, X.; Yun, H. S.; Kwon, Y. J.; Lee, S. K; Choi, J. -W.; Zhao, L. X. “ First Synthesis of 4 -Selenonucleosides Showing Unusual Southern Conformation” Organic Letters 2008, 10, 209-212.

19. Jeong, L. S.; Tosh, D. K.; Choi, W. J.; Pal, S. “Synthesis of Fluoroneplanocine A” Current Protocols in Nucleic Acid Chemistry (John Wiley & Son, Inc. Publication) 2008, 14.6.1-14.6.18.

20. Jeong, L. S.; Pal, S.; Choe, S.A.; Choi, W.J.; Jacobson, K.A.; Gao, Z.G.; Klutz, A.M.; Hou, X.; Kim, H.O.; Lee, H.W.; Lee, S.K.; Tosh, D.K.; Moon, H.R. “Structure activity relationships of truncated D- and L- 4'-thioadenosine derivatives as species-independent A3 adenosine receptor antagonists” Journal of Medicinal Chemistry 2008, 51, 6609-6613.

21. Jeong, L. S.; Choi, Y.; Tosh, D. K.; Choi, W. J.; Kim, H. O.; Choi, J “ Design and synthesis of novel 2',3'-dideoxy-4'-selenonucleosides as potential antiviral agents” Bioorganic Medicinal Chemistry 2008, 16, 9891-9897.

22. Jeong, L. S.; Lee, H. W.; Kim, H. O.; Tosh, D. K.; Pal, S.; Choi, W. J.; Gao, Z. G.; Patel, A. R.; Williams, W.; Jacobson, K. A.; Kim, H. D. “ Structure-Activity Relationships of 2-Chloro-N6-substituted-4'-thioadenosine-5'-N,N-dialkyluronamides as the Human A3 Adenosine Receptor Antagonists” Bioorganic Medicinal Chemistry Letters 2008, 18, 1612-1616.

23. Lee, H.; Tosh, D. K., Choi, W. J.; Kim, Y. M.; Lee, S. K.; Jeong, L. S. “Synthesis and Antitumor Activity of 1-β-Selenoarabinofuranosyl cytosine (4 -Seleno-ara-C) Nucleic Acids Symposium Series 2008, 52, 639-640.

24. Singh, V.; Singh, R. B.; Tosh, D. K.; Mobin, S. M. “Cycloaddition of Cyclohexa-2,4-dienones with Nitroolefins: An unusual regio-selectivity. An Expeditious entry into Nitro Bicyclo[2.2.2]octenones” Synthetic Communication 2008, 38, 3112-3120.

25. Singh, V.; Pal, S.; Tosh, D. K.; Mobin, S. M. “Molecular complexity from Aromatics. Cycloaddition of cyclohexa-2,4-dienones, sigmatropic 1,2-acyl shift and ring-closing metathesis: a new, efficient and stereoselective synthesis of ( )-hirsutic acid C and medium ring carbocycles” Tetrahedron 2007, 63, 2446-2454.

26. Wang, T.; Lee, H. J.; Tosh, D. K.; Kim, H. O.; Pal, S.; Choi, S.; Lee, Y.; Moon, H. R.; Zhao, L. X.; Lee, K. M.; Jeong, L. S. “Design, Synthesis, and Molecular Modeling Studies of 5 -Deoxy-5 -ureidoadenosine: 5 -Ureido Group as a Multiple Hydrogen Bonding Donor in the Active Site of S-Adenosylhomocysteine Hydrolase”.Bioorganic Medicinal Chemistry Letters 2007, 17, 4456-4459.

27. Hou, X.; Lee, H. W.; Tosh, D. K.; Zhao, L. X.; Jeong, L. S. “Alternative and Improved Syntheses of Highly Potent and Selective A3 Adenosine Receptor Agonists, Cl-IB-MECA and Thio-Cl-IB-MECA” Archive of Pharmacal Research 2007, 30, 1205-1209.

28. Jeong, L. S.; Choe, S. A.; Gunaga, P.; Kim, H. O.; Lee, H. W.; Lee, S. K.; Tosh, D. K.; Patel, A.; Palaniappan, K. K.; Gao, Z. G.; Jacobson, K. A.; Moon, H. R. “ Discovery of a New Nucleoside Template for Human A3 Adenosine Receptor Ligands: D-4'-Thioadenosine Derivatives without 4'-Hydroxymethyl Group as Highly Potent and Selective Antagonists” Journal of Medicinal Chemistry 2007, 50, 3159-3162.

29. Jeong, L. S.; Lee, J. A.; Kim, H. O.; Tosh, D. K.; Moon, H. R.; Lee, S. J.; Lee, K. M.; Sheen, Y. Y.; Chun, M. W. “Asymmetric Synthesis of Cyclopropyl-fused 2'-C-Methylcarbanucleosides as Potential Anti-HCV Agents” Nucleosides, Nucleotides and Nucleic Acids 2007, 26, 1021-1024.

30. Jeong, L. S.; Gunaga, P.; Kim, H. O.; Tosh, D. K.; Lee, H. W.; Choe, S. A.; Moon, H. R.; Gao, Z. G.; Jacobson, K. A. “Stereoselective Synthesis of 1 -Functionlized-4 -Thionucleosides” Nucleosides, Nucleotides and Nucleic Acids 2007, 26, 1011-1014.

31. Lee, J. A.; Kim, H. O.; Tosh, D. K.; Moon, H. R.; Kim, S.; Jeong, L. S. “Stereoselective Synthesis of 2 -C-Methyl-Cyclopropyl Fused Carbanucleosides as Potential Anti-HCV Agents” Organic Letters 2006, 8, 5081-5083.

32. Gunaga, P.; Kim, H. O.; Lee, H. W.; Tosh, D. K.; Ryu, J. S.; Choi, S.; Jeong, L. S. “Stereoselective Functionalization of the 1 -Position of 4 -Thionucleosides” Organic Lettesr 2006, 8, 4267-4270.

33. Singh, V.; Tosh, D. K.; Mobin, S. M. “Synthesis of embellished bicyclo[2.2.2] octenones and a sigmatropic 1,2-acyl shift in an excited state: a novel and stereoselective route to ( )-hirsutic acid C and complicatic acid” Tetrahedron Letters 2004, 45, 1729-1732.

34. Singh, V.; Tosh, D. K. “Molecular complexity from aromatics: Synthesis of embellished endo tricyclo[5.2.2.02,6]undecanes” Indian Journal of Chemistry 2003, 42B, 873-875.

35. Singh, V.; Tosh, D. K.; Kane, V. V.; Ernst, L; Jones, P. G. “Cycloaddition of substituted spiroepoxycyclohexa-2,4-dienones: synthesis and X-ray crystal structure of the adducts” Tetrahedron Letters 2002, 43, 5775-5777.

36. Bardhan, M.; Tosh, D. K.; Panda, C. S.; Padhy, A. K. “Synthesis and Reactions of 1-amino-2-arylimidazolin-5-ones” Journal of Teaching and Research in Chemistry 1999, 6, 9-14.

BOOK CHAPTERS

1. Tosh, D. K.; Kim, H. O.; Pal, S.; Lee, J. A.; Jeong, L. S. “ Synthesis and Biological Activity of Neplanocin and its analogues” Modified Nucleosides: in Biochemistry, Biotechnology and Medicine (Prof. Piet Herdewijn, (Editor), John Wiley & Son, Inc. Publication) Chapter 20, 2008, pp 497-538.

2. Jacobson, K. A.; Klutz, A. M.; Tosh, D. K.; Ivanov, A. A.; Preti, D.; Baraldi, P. G. “Medicinal Chemistry of A3 Adenosine Receptor: Agonists, Antagonists and receptor Engineering” Adenosine Receptors in Health and Diseases, Handbook of Experimental Pharmacology (C. N. Wilson and S. J. Mustafa (editors), Springer-Verlag Berlin Heidelberg Publication) 2009, vol. 193, pp 123-159.

3. Jacobson, K. A.; Gao, Z. G.; Tosh, D. K.; Sanjayan, G. J.; de Castro, S. “A3 Adenosine Receptor Agonist: History and Future Perspectives” A3 Adenosine Receptors from cell Biology to Pharmacology and Therapeutics (P. A. Borea (editor), Springer Netherlands Publication) 2009, pp 93-120.

ORAL PRESENTATIONS

1. Dilip K. Tosh “Studies on Development of A3 Adenosine receptor Ligands

and Discovery of Next Generation Nucleosides” LaserGen Inc., Houston, Texas, USA, 31st July 2010.

2. Dilip K. Tosh “Discovery of 4 -Seleno nucleosides as a next generation nucleosides having unusual conformation and development of A3 adenosine receptor agonist and antagonist”; 11th Sept. 2008, NIDDK, National Institute of Health, Bethesda, Maryland, USA.

3. Dilip K. Tosh, S. A. Choe, P. Gunaga, H. O. Kim, Lak Shin Jeong “ Development of Novel Human A3 Adenosine Receptor Antagonists” ; New Horrizone of Medicinal Chemistry, 20th June 2007, Anmyundo Ocean Castle, South Korea.

4. Dilip K. Tosh and V. Singh and “Cycloaddition of cyclohexa-2,4-dienones and electron poor 2π partner and photochemical 1,2-acyl shoft: a novel synthesis of hirsutic acid’’ 2nd In house symposium, Indian Institue of Technology, Bombay, India April 2003.

POSTER PRESENTATIONS

• Tosh, D. K.; Phan, K.; Deflorian, F.; Wei, Q.; Gao, Z.-G.; Jacobson, K. A. “Discovery of truncated (N)-methanocarba nucleosides as A1 adenosine receptor agonists” 243rd ACS national meeting; March 25th-29th, 2012, San Diego; MEDI-136.

• Jacobson, K. A.; Stevens, R. C.; Abagyan, R.; Deflorian, F.; Gao, Z.-G.; Gakh, A. A.; Tosh, D. K.; Kumar, T. S.; Xu, F.; Katritch, V. “ Structure-based adenosine receptor ligands” 243rd ACS national meeting; March 25th-29th, 2012, San Diego; MEDI-275.

• Tosh, D. K.; Chanyshev, B.; Isak, A.; Chepurko, Y.; Phan, K.; Hochhauser, E.; Shainberg, A.; Jacobson, K. A. “Discovery of novel polyamidoamine (PAMAM) dendrimer conjugated A3 adenosine receptor agonist ligand as a cardioprotective agent” 242nd ACS national meeting; August 28th-September 1st, 2011, Denver, USA, MEDI-355.

• Balasubramanian, R.; Tosh, D. K.; Lloyd, J. R.; Gao, Z .-G.; Jacobson, K. A. “Characterization of fluorescent GPCR-ligand dendrimer (GLiDe) conjugates in binding to the A3 adenosine receptors” Experimental Biology meeting; April 9-13, 2011, Washington DC.

• Tosh, D. K.; Yoo, L. S.; Chinn, M.; Gao, Z. –G.; Jacobson, K. A. “Strategy for conjugation of "clickable" agonists of the A3 adenosine receptor to polyamidoamine (PAMAM) dendrimers” 240th ACS national meeting; August 22-26th, 2010, Boston, USA, MEDI-220.

• Tosh, D. K.; Chinn, M.; Ivanov, A. A.; Gao, Z. –G.; Jacobson, K. A. “ Functionalized Congers of A3 adenosine receptor selective nucleosides” 238th ACS national meeting; August 16-20th, 2009, Washington, D. C., USA, MEDI-174.

• Maruoka, H.; Ko, H.; Tosh, D. K.; Melman, A.; Carter, R. L.; Costanzi, S.; Harden, T. K.; Jacobson, K. A. “ Selective P2Y6 receptor agonists: Extended phosphate and (S)-methanocarba ribonucleotides analogs” 238th ACS national meeting; August 16-20th, 2009, Washington, D. C., USA, MEDI-187.

• Ivanov, A. A.; Tosh, D. K.; Gao, Z. –G.; Chinn, M.; Jacobson, K. A. “Macromolecular ligands for G protein-coupled receptors: Biotin functionalized congeners complexed with streptavidin as agonist probes for the A3 adenosine receptor” 238th ACS national meeting; August 16-20th, 2009, Washington, D. C., USA, MEDI-410.

References

1. Dr. Kenneth A. Jacobson

Chief, Molecular Recognition Section,

Laboratory of Bioorganic Chemistry,

National Institute of Diabetes and Digestive and Kidney Diseases,

National Institute of Health, Bldg. 8A, Rm. B1A-19

Bethesda, Maryland 20892 USA

Phone: +1-301-***-****

Fax: +1-301-***-****

Email: vcgt98@r.postjobfree.com

2. Prof. Lak Shin Jeong

Laboratory of Medicinal Chemistry,