Dr Jonathan Baell
Details
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Division: Structural Biology
Research Overview
Our laboratory focuses on all aspects of medicinal chemistry. Because of our translational vocation, we are positioned at the crossroad between biology, structural biology and chemistry and we pursue both focused drug discovery activities as well as academic basic research. Through private/public collaborations, via the CRC for Cancer therapeutics and other institutions, we develop new biologically active small molecules in areas relevant for the treatment of diseases such as cancer and tropical diseases.
Our academically oriented research axis is aimed at understanding and targeting protein-protein interactions. We are interested in the design of peptidomimetics and the study of their interactions with their cognate receptors. These studies include conformational analysis, molecular recognition and chemical biology. Finally, we are also interested in the efficient synthesis of biologically active natural products to provide amenable access to structure activity relationship studies.
Research Projects
Bcl-2 proteins and the apoptotic machinery:
- Benzoylureas and benzothiazoles as peptidomimetic scaffolds
- Small molecule inhibitors of Mcl-1
- Small molecule inhibitors of Bcl-xL
- Small molecule anti-parasitic agents
Conformational analysis of peptidomimetics
Natural product synthesis: spiroleucettadine and spirocalcaridine
Development of new selection criteria for quality high throughput screening libraries
Major Publications
- Lessene G, Czabotar P, Colman PM
Bcl-2 family antagonists for cancer therapy,
Nat. Rev. Drug Discov. 2008, 7(12): 989-1000. - Harvey AJ, Baell JB, Toovey N, Homerick D, Wulff H.
A new class of blockers of the voltage-gated potassium channel Kv1.3 via modification of the 4- or 7-position of khellinone.
J Med Chem. 2006 Feb 23;49(4):1433-41 PMID: 16480279 [PubMed - indexed for MEDLINE] - Aberle NS, Lessene G, Watson KG.
A concise total synthesis of naamidine A.
Org Lett. 2006 Feb 2;8(3):419-21 PMID: 16435849 [PubMed - indexed for MEDLINE] - Baell JB, Gable RW, Harvey AJ, Toovey N, Herzog T, Hänsel W, Wulff H.
Khellinone derivatives as blockers of the voltage-gated potassium channel Kv1.3: synthesis and immunosuppressive activity.
J Med Chem. 2004 Apr 22;47(9):2326-36 PMID: 15084131 [PubMed - indexed for MEDLINE] - Pietersz GA, Mottram PL, van de Velde NC, Sardjono CT, Esparon S, Ramsland PA, Moloney G, Baell JB, McCarthy TD, Matthews BR, Powell MS, Hogarth PM.
Inhibition of destructive autoimmune arthritis in FcgammaRIIa transgenic mice by small chemical entities.
Immunol Cell Biol. 2009 Jan;87(1):3-12 PMID: 19030019 [PubMed - in process] - Lessene G, Czabotar PE, Colman PM
Bcl-2 family antagonists for cancer therapy
Nat. Rev. Drug Discov. 2008, 7(12): 989-1000. - Cianci J, Baell JB, Flynn BL, Gable RW, Mould JA, Paul D, Harvey AJ.
Synthesis and biological evaluation of chalcones as inhibitors of the voltage-gated potassium channel Kv1.3.
Bioorg Med Chem Lett. 2008 Mar 15;18(6):2055-61 PMID: 18289849 [PubMed - indexed for MEDLINE] - Aberle N, Catimel J, Nice EC, Watson KG.
Synthesis and biological evaluation of analogues of the anti-tumor alkaloid naamidine A.
Bioorg Med Chem Lett. 2007 Jul 1;17(13):3741-4 PMID: 17462892 [PubMed - indexed for MEDLINE] - Ferens D, Baell J, Lessene G, Smith JE, Furness JB.
Effects of modulators of Ca(2+)-activated, intermediate-conductance potassium channels on motility of the rat small intestine, in vivo.
Neurogastroenterol Motil. 2007 May;19(5):383-9 PMID: 17509020 [PubMed - indexed for MEDLINE] - Nguyen TV, Matsuyama H, Baell J, Hunne B, Fowler CJ, Smith JE, Nurgali K, Furness JB.
Effects of compounds that influence IK (KCNN4) channels on afterhyperpolarizing potentials, and determination of IK channel sequence, in guinea pig enteric neurons.
J Neurophysiol. 2007 Mar;97(3):2024-31 PMID: 17229825 [PubMed - indexed for MEDLINE]
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Current Laboratory Members
Faculty Member: Keith Watson, BSc(Hons) PhD Mon
Faculty Member: Jonathan Baell, BSc(Hons) UTAS PhD Melb
Faculty Member: Guillaume Lessene, PhD Bordeaux 1
Senior Postdoctoral Fellow: Chinh Bui, BSc(Hons) Griffith PhD Melb
Senior Postdoctoral Fellow: Brad Sleebs, BSc(Hons) PhD LaT
Postdoctoral Fellow: Danny Ganame, BSc(Hons) LaT PhD Melb
Postdoctoral Fellow: Georgina Holloway, BAppSc(Hons) RMIT PhD Melb
Postdoctoral Fellow: George Nikolakopoulos, BAppSc(Hons) QUT PhD Mon
Postdoctoral Fellow: Jean-Jacques Youte, PhD France
Research Technician: Wilco Kersten, BSc Netherlands
Research Technician: Dana Stachurska-Buczek, MSc Poland
Research Technician: Yelena Khakham, Bsc(Hons) Mon
Postgraduate Student: Ryan Brady, BSc Melb
Postgraduate Student: Theola Louie, BMedChem(Hons) Mon
Postgraduate Student: Jelena Medan, Bsc(Hons) LaTrobe
Undergraduate Student: Duong Nhu
Undergraduate Student: Kung Ban