Laura Heitman | Medicinal Chemistry

Laura Heitman, Ph.D.

Position:

Assistant professor of medicinal chemistry

Telephone number: +31 (0)71 527 4558
E-mail address: l.h.heitman@lacdr.leidenuniv.nl
Faculty/Unit: Faculty of Science, Leiden Academic Centre for Drug Research, Medicinal Chemistry
Office address: Gorlaeus Laboratories
Einsteinweg 55
2333 CC Leiden
roomnumber L-061

Biography

I studied Biopharmaceutical Sciences at Leiden University from September 1999 until October 2004. In the last two years of my education I have done three internships. Two of them were at the division of Medicinal Chemistry in Leiden. The first one was organic chemistry based and the second had a biology / pharmacology flavor. For the third internship I went to London, where I worked at the department of Pharmaceutical and Biological Chemistry at the School of Pharmacy of the University of London for 5 months. Here I definitely learned that my interest was more in the molecular biology / pharmacology area, especially dealing with receptors.

Subsequently, I performed my PhD research at the Division of Medicinal Chemistry of Leiden University under supervision of Prof. Dr. A. P. IJzerman and in collaboration with MSD (former Organon, Oss, NL) as part of the Top Institute Pharma (TI Pharma) consortium. Here I gained knowledge on allosteric modulation of adenosine receptors and ‘reproductive’ GPCRs (GnRH and LH receptor). This has led to a scientific ‘output’ of eleven articles and two patents. I have presented my research at several (inter)national congresses and received five prizes. Moreover, I was named “Discoverer of the Year 2009” by the C.J. Kok-jury of the Faculty of Science for her scientific achievements.

All this resulted in a position as assistant professor for Molecular Pharmacology at the Division of Medicinal Chemistry (Leiden) in January 2009. Due to my extensive experience on (in vitro) ligand kinetics, I continue to focus on the importance thereof in drug discovery. In this respect, I have introduced a new research topic to the division, namely drug-target residence time.
In general, my areas of interest include the molecular pharmacology of ligand-receptor interactions, and more specifically, allosteric modulation of GPCRs and receptor residence time. Due to my recently (July 2010) obtained VENI grant from the Netherlands Organisation for Scientific Research (NWO), these topics are being studied more deeply. More on these interesting topics can be found on our website under ‘Research/Novel Receptor Concepts’.

2012

Guo, D., Van Dorp, E.J.H., Mulder-Krieger, T., Van Veldhoven, J.P.D., Brussee, J., IJzerman, A.P., Heitman, L.H. , Dual-Point Competition Association Assay: A Fast and High-Throughput Kinetic Screening Method for Assessing Ligand-Receptor Binding Kinetics, Journal of Biomolecular Screening, vol. 17, issue 9. DOI

Heitman, L.H., Kleinau, G., Brussee, J., Krause, G., IJzerman, A.P. , Determination of different putative allosteric binding pockets at the lutropin receptor by using diverse drug-like low molecular weight ligands, Mol Cell Endocrinol, vol. 351, issue 2, pp. 326-36. DOI

Guo, D., Mulder-Krieger, T., IJzerman, A.P., Heitman, L.H. , Functional efficacy of adenosine A2A receptor agonists is positively correlated to their receptor residence time, Br J Pharmacol, issue 166, pp. 1846-59. DOI

Chen, D., Errey, J.C., Heitman, L.H., Marshall, F.H., IJzerman, A.P., Siegal, G. , Fragment screening of GPCRs using biophysical methods: identification of ligands of the adenosine A(2A) receptor with novel biological activity, ACS Chem Biol, vol. 7, issue 12, pp. 2064-73. DOI

Watts, A.O., Scholten, D.J., Heitman, L.H., Vischer, H.F., Leurs, R. , Label-free impedance responses of endogenous and synthetic chemokine receptor CXCR3 agonists correlate with Gi-protein pathway activation, Biochem Biophys Res Commun, vol. 419, issue 2, pp. 412-8. DOI

Liu_W.,, Chun, E., Thompson, A.A., Chubukov, P., Xu, F., Katritch, V., Han, G.W., Roth, C.B., Heitman, L.H., IJzerman, A.P., Cherezov, V., Stevens, R.C. , Structural basis for allosteric regulation of GPCRs by sodium ions, Science, vol. 337, issue 6091, pp. 232-6. DOI

2011

Heitman, L.H., Kleinau, G., Krause, G., Brussee, J., IJzerman, A.P. , Identification of a second allosteric site at the luteinizing hormone receptor that recognizes both allosteric enhancers and inhibitors, British Journal of Pharmacology.

2009

Heitman, L.H., Göblyös, A., Zweemer, A.M., Bakker, R., Mulder-Krieger, T., Van Veldhoven, J.P.D., De Vries, H., Brussee, J., IJzerman, A.P. , A Series of 2,4-Disubstituted Quinolines as a New Class of Allosteric Enhancers of the Adenosine A(3) Receptor, Journal of Medicinal Chemistry, vol. 52, no. 4, pp. 926-931.

Heitman, L.H., Narlawar, R., de Vries, H., Willemsen, M.N., Wolfram, D., Brussee, J., IJzerman, A.P. , Substituted Terphenyl Compounds as the First Class of Low Molecular Weight Allosteric Inhibitors of the Luteinizing Hormone Receptor, Journal of Medicinal Chemistry, vol. 52, no. 7, pp. 2036-2042.

Bonger, K.M., van den Berg, R.J.B.H.N., Knijnenburg, Annemiek D., Heitman, Laura H., van Koppen, Chris J., Timmers, Cornelis M., Overkleeft, Herman S., van der Marel, Gijsbert A. , Discovery of Selective Luteinizing Hormone Receptor Agonists Using the Bivalent Ligand Method, ChemMedChem, vol. 4, no. 7, pp. 1189-1195.

2008

Heitman, L.H., Ye, K., Oosterom, J., IJzerman, A.P. , Amiloride derivatives and a nonpeptidic antagonist bind at two distinct allosteric sites in the human gonadotropin-releasing hormone receptor, Molecular Pharmacology, vol. 73, no. 6, pp. 1808-15.

Heitman, L.H., van Veldhoven, J.P.D., Zweemer, A.M., Ye, K., Brussee, J., IJzerman, A.P. , False positives in a reporter gene assay: identification and synthesis of substituted N-pyridin-2-ylbenzamides as competitive inhibitors of firefly luciferase, Journal of Medicinal Chemistry, vol. 51, no. 15, pp. 4724-9.

Heitman, L.H., IJzerman, A.P. , G protein-coupled receptors of the hypothalamic-pituitary-gonadal axis: a case for Gnrh, LH, FSH, and GPR54 receptor ligands, Medicinal Research Reviews, vol. 28, no. 6, pp. 975-1011.

Bonger, K.M., van den Berg, R.J.B.H.N., Knijnenburg, A.D., Heitman, L.H., IJzerman, A.P., Oosterom, J., Timmers, C.M., Overkleeft, H.S., van der Marel, G.A. , Synthesis and evaluation of homodimeric GnRHR antagonists having a rigid bis-propargylated benzene core, Bioorganic & Medicinal Chemistry, vol. 16, no. 7, pp. 3744-58.

Heitman, L.H., Oosterom, J., Bonger, K.M., Timmers, C.M., Wiegerinck, P.H.G., IJzerman, A.P. , [3H]Org 43553, the first low-molecular-weight agonistic and allosteric radioligand for the human luteinizing hormone receptor, Molecular Pharmacology, vol. 73, no. 2, pp. 518-24.

2007

Bonger, K.M., van den Berg, R.J.B.H.N., Heitman, L.H., IJzerman, A.P., Oosterom, J., Timmers, C.M., Overkleeft, H.S., van der Marel, G.A. , Synthesis and evaluation of homo-bivalent GnRHR ligands, Bioorganic & Medicinal Chemistry, vol. 15, no. 14, pp. 4841-56.

2006

Heitman, L.H., Mulder-Krieger, T., Spanjersberg, R.F., von Frijtag Drabbe Künzel, J.K., Dalpiaz, A., IJzerman, A.P. , Allosteric modulation, thermodynamics and binding to wild-type and mutant (T277A) adenosine A1 receptors of LUF5831, a novel nonadenosine-like agonist, British Journal of Pharmacology, vol. 147, no. 5, pp. 533-41.

2004

van den Nieuwendijk, A.M.C.H., Pietra, D., Heitman, L., Göblyös, A., IJzerman, A.P. , Synthesis and biological evaluation of 2,3,5-substituted [1,2,4]thiadiazoles as allosteric modulators of adenosine receptors, Journal of Medicinal Chemistry, vol. 47, no. 3, pp. 663-72.

Laura currently supervises the following students:

10/01/2011

Medicinal Chemistry

Laura Heitman, Ph.D.

Biography

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