- B.S. (2001), The Hebrew University of Jerusalem;
- MBA (2005), The Hebrew University of Jerusalem;
- M.S. (2006) The Hebrew University of Jerusalem (Chaim Gilon);
- Ph.D. (2011), The Hebrew University of Jerusalem (Chaim Gilon & Alexander Levitzki);
- Postdoctoral Research Associate (2011-2014), University of Wisconsin-Madison (Helen E. Blackwell)
Research in the Tal-Gan laboratory will focus on the development of chemical-based tools to address important biological questions with potential therapeutic implications. There is a constant demand for new and improved chemical probes that can be utilized to study diverse biological systems, and peptides represent attractive tools for the generation of such probes. My lab will use peptides and their analogs to study important signaling pathways and develop novel drug-leads. Two main areas of research will be insulin and bacterial communication.
Insulin is a 51-amino acid globular protein produced by the pancreas to regulate glucose levels in the blood. Although insulin has been the subject of considerable research efforts in the past 50 years, still many questions remain about this fascinating molecule and its structure-function relationships. Using peptidomimetics and protein synthesis techniques, my lab will design novel insulin analogs containing non-natural building blocks to answer fundamental questions regarding insulin.
Alternative approaches for antimicrobial therapy
Bacteria utilize chemical signals to communicate and synchronize their behavior. These signals enable bacteria to assess their environments and population densities, and thus adapt quickly to internal or external changes. The diverse signaling pathways are used by bacteria to behave as multicellular organisms either by collectively turning on group-beneficial phenotypes at high cell density or by sacrificing individual bacterium to secure the survival of the colony in stressful conditions. My lab will use two different approaches to combat bacterial infections by intercepting bacterial signaling pathways. The first approach will be to develop pathogen-specific antibiotics that only kill the target pathogen without harming the natural human microflora. The second approach will be to attenuate phenotypes associated with pathogen infectivity (such as virulence factor production and biofilm formation) without killing the bacteria, thus reducing the selective pressure for resistance.
The interdisciplinary research in the Tal-Gan lab will include the development of efficient synthetic pathways for the construction of various peptidomimetics and the application of these compounds to the characterization and treatment of various disease states using state-of-the-art biological screening techniques.
- Tal-Gan, Y.; Stacy, D.M.; Blackwell, H.E. N-Methyl and Peptoid Scans of an Autoinducing Peptide Reveal New Structural Features Required for Inhibition and Activation of AgrC Quorum Sensing Receptors in Staphylococcus aureus. Chem. Commun. 2014, 50, 3000-3003.
- Broderick, A.H.; Stacy, D.M.; Tal-Gan, Y.; Kratochvil, M.J.; Blackwell, H.E.; Lynn, D.M. Surface Coatings that Promote Rapid Release of Peptide-Based AgrC Inhibitors for Attenuation of Quorum Sensing in Staphylococcus aureus. Adv. Healthcare Mater. 2014, 3, 97-105.
- Tal-Gan, Y.; Ivancic, M.; Cornilescu, G.; Cornilescu, C.C.; Blackwell, H.E. Structural Characterization of Native Autoinducing Peptides and Abiotic Analogs Reveals Key Features Essential for Activation and Inhibition of an AgrC Quorum Sensing Receptor in Staphylococcus aureus. J. Am. Chem. Soc. 2013, 135, 18436-18444.
- Tal-Gan, Y.; Stacy, D.M.; Foegen, M.K.; Koenig, D.W.; Blackwell, H.E. Highly Potent Inhibitors of Quorum Sensing in Staphylococcus aureus Revealed through a Systematic Synthetic Study of the Group-III Autoinducing Peptide. J. Am. Chem. Soc. 2013, 135, 7869-7882.
- Hurevich, M.; Ratner-Hurevich, M.; Tal-Gan, Y.; Shalev, D.E.; Ben-Sasson, S.Z.; Gilon, C. Backbone Cyclic Helix Mimetic of Chemokine (C-C Motif) Receptor 2: A Rational Approach for Inhibiting Dimerization of G Protein-Coupled Receptors. Bioorg. Med. Chem. 2013, 21, 3958-3966.
- Horwitz, E.; Tal-Gan, Y.; Temper, V.; Shapiro, M.; Gilon, C.; Hoffman, A. Chemical trapping of vancomycin - a potential strategy for preventing selection of vancomycin-resistant Enterococci. Microb. Drug Resist. 2012, 18, 109-115.
- Tal-Gan, Y.; Naveh, S.; Klein, S.; Moshel, O.; Levitzki, A.; Gilon, C. Studying Protein-Peptide Interactions Using Benzophenone Units: A Case Study of PKB/Akt and its Inhibitor PTR6154. Anal. Biochem. 2012, 421, 750-754.
- Naveh, S.; Tal-Gan, Y.; Ling, S.; Hoffman, A.; Holoshitz, J.; Gilon, C. Developing Potent Backbone Cyclic Peptides Bearing the Shared Epitope Sequence as Rheumatoid Arthritis Drug-Leads. Bioorg. Med. Chem. Lett. 2012, 22, 493-496.
- Tal-Gan, Y.; Freeman, N.S.; Klein, S.; Levitzki, A.; Gilon, C. Metabolic Stability of Peptidomimetics: N-Methyl and Aza Heptapeptide Analogs of a PKB/Akt Inhibitor. Chem. Biol. Drug Des. 2011, 78, 887-892.
- Tal-Gan, Y.; Hurevich, M.; Klein, S.; Ben-Shimon, A.; Rosenthal, D.; Hazan, C.; Shalev, D.E.; Niv, M.Y.; Levitzki, A.; Gilon, C. Backbone-Cyclic Peptide Inhibitors of Protein Kinase B (PKB/Akt). J. Med. Chem. 2011, 54, 5154-5164.
- Freeman, N.S.; Tal-Gan, Y.; Klein, S.; Levitzki, A.; Gilon, C. Microwave-Assisted Solid-Phase Aza-peptide Synthesis: Aza Scan of a PKB/Akt Inhibitor Using Aza-arginine and Aza-proline Precursors. J. Org. Chem. 2011, 76, 3078-3085.
- Tal-Gan, Y.; Freeman, N.S.; Klein, S.; Levitzki, A.; Gilon, C. Synthesis and structure-activity relationship studies of peptidomimetic PKB/Akt inhibitors: The significance of backbone interactions. Bioorg. Med. Chem. 2010, 18, 2976-2985.
- Hurevich, M.; Tal-Gan, Y.; Klein, S.; Barda, Y.; Levitzki, A.; Gilon, C. Novel method for the synthesis of urea backbone cyclic peptides using new Alloc protected glycine building units. J. Pept. Sci. 2010, 16, 178-185.