Dr Paul R Jenkins

Senior Lecturer in Organic Chemistry

B.Sc., Ph.D. (Wales).

Tel: 0116 252 2124

email: kin@le.ac.uk

Research Interests

Research is being carried out in the area of synthetic organic chemistry.  The general plan is to design and synthesise new molecules that have anti-cancer or glycosidase inhibition activity.

Cancer Chemistry

We are taking a new approach to developing new agents for cancer chemotherapy.  We have discovered small molecules which are non-toxic and which intervene in the controlling pathways of cell division.  These compounds are inhibitors of the check-point kinase CDK4.  The project is funded by CRUK.  The picture below shows our best inhibitor in the active site of a homology model of CDK4.  We have used novel photochemistry and Suzuki coupling reactions to produce a library of CDK 4 inhibitors all of which show selectivity for CDK4 over CDK2.  Future projects will be focused on the refinement and improvement of our most active compounds.

A new inhibitor docked into the active site of a CDK4 homology model.

Carbohydrate Chemistry

NEW PROJECTS:
Studies on a novel tryptophan halogenase

This is a collaboration with Dr M. Clockie in the department of Infection, Immunity and Inflamation.  The work involves molecular biology and chemistry combining to study the production and mechanism of a new halogenase enzyme and its possible application in synthetic chemistry for the synthesis of anti-cancer compounds.

The synthesis and cancer preventive activity of new molecules based on natural products

This is a collaboration with Professors A. Gescher and W. Steward of the department of Cancer Studies and Molecular Medicine.

Selected Publications

1. “Diindolyl fascaplysin-inspired inhibitors of CDK4/cyclin D1: A new strategy for selectivity.”  Carine Aubry, A. James Wilson, Daniel P. G. Emmerson, Emma Murphy, Yu Yam Chan, Michael P. Dickens, Marcos D. García, Paul R. Jenkins,* Sachin Mahale, Bhabatosh Chaudhuri.  Bioorganic & Medicinal Chemistry, 2009, 17, 6073-6084.
2.  “Steroselective Synthesis by Double Reductive Amination Ring Closure of Novel Aza-Heteroannulated Sugars.”  Dominic L. Laventine, Paul M. Cullis, Marcos D. García and Paul R. Jenkins.* Tetrahedron 65 (2009), pp. 4766-4774.
3. “Stereoselective synthesis of 7-membered lactams and lactones on a carbohydrate scaffold using ring-closing metathesis.”  Dominic L. Laventine, Paul M. Cullis, Marcos D. García and Paul R. Jenkins.* Tetrahedron Letters, 2009, 50, 3557-3660. 
4.  “Reassessment of the Reaction Mechanism in the Heme Dioxygenases.”  N. Chauhan, S.J. Thackray, S.A. Rafice, G. Eaton, M. Lee, I. Efimov, J. Basran, P.R. Jenkins, C. Mowat, S.K. Chapman and E. Lloyd Raven.  J.Am.Chem.Soc., 2009, 131 (12) 4186-4187.
5. " Design, synthesis and biological evaluation of new tryptamine and tetrahydro-.beta.-carboline-based selective inhibitors of CDK4.”  Jenkins, Paul R.*; Wilson, James; Emmerson, Daniel; Garcia, Marcos D.; Smith, Matthew R.; Gray, Stephen J.; Britton, Robert G.; Mahale, Sachin; Chaudhuri, Bhabatosh. Bioorganic & Medicinal Chemistry  (2008),  16(16),7728-7739.
6. “Synthesis, crystal structure and biological activity of b-carboline based selective CDK4-cyclin D1 inhibitors.”  M.D. García, A.J. Wilson, D.P.G. Emmerson, P.R. Jenkins*, S. Mahale and B. Chaudhuri, Org. Biomol. Chem., 2006, 4, 4478 - 4484.
7. "CA224 a non-planar analogue of of fascaplysin, inhibits CDK4 specifically and arrests cells at  G0/G1 inhibiting pRB phosphorylation." S. Mahale, C. Aubry, J. Wilson, P.R. Jenkins, B. Chaudhuri*, J.-D. Marechal and M.J. Sutcliffe, Bio and Med Chem Lett., 2006, 16. 4272-4278.
8. "Inhibition of cancer cell growth by CDK4 inhibitors synthesised based on the structure of fascaplysin." S. Mahale, C. Aubry, J. Wilson, P.R. Jenkins, B. Chaudhuri*, J.-D. Marechal and M.J. Sutcliffe, Bioorganic Chemistry., 2006, 34, 5, 287-297.
9. “Synthesis, glycosidase activity and X-ray crystallography of 3-aminosugars.” V.L. Maxwell, E.L. Evinson, D.P.G. Emmerson and P.R. Jenkins*, Organic and Biological Chemistry, 2006, 4, 2724-2732.
10. “Regioselective photo-oxidation of 1-benzyl-4,9-dihydro-3H-b-carbolines,”
    M. D. García, A. J. Wilson, D. P. G. Emmerson and P. R. Jenkins,* Chem Commun., 2006, 2586-2588.
11. “Diasterocontrol in the intramolecular meta-photocycloaddition of arenes and olefines
    R. C. Morales, A. Lopez-Mosquera, N. Roper, P. R. Jenkins,* J. Fawcett and M. D. García, Photchem Photobiology, 2006, 5, 649-652.
12. “Design, synthesis and biological activity of new CDK4-specific inhibitors based on fascaplysin,” C. Aubry, J. Wilson, P.R. Jenkins*, S. Mahale, B. Chaudhuri, J.-D. Marechal and M.J. Sutcliffe, Organic and Biological Chemistry, 2006, 4, 787.