Research Synopsis: Synthesis, catalysis and chemical biology of small molecules, nucleic acids, peptides and lipids.
1. Bottom-Up Liposome Engineering
Compartmentalization is vital for cellular defense, transportation and communication. We are interested in spontaneous formation of simple yet functional membrane models (aka liposomes) under bio-orthogonal conditions. We aim to apply these models to study chemical catalysis, protein expression and to develop methods for detecting critical human diseases.
2. Anti-Viral Drug Development
Modified nucleotides are important biomarkers of inflammation and oxidative stress. In the presence of dysfunctional repair mechanisms, accumulation of these molecules can cause mutations, which are believed to contribute to cancer, neurodegenerative disorders and premature aging. These nucleotides competitively bind to a growing chain of genetic material, causing mutations or stalling the replication. Through computational modeling, organic synthesis and replication assays, we aim to develop anti-viral drugs that work by the same mode of action and purposely induce mutations in viral genome.
3. Nucleic Acid Research
Nucleic acids (especially RNA) can fold into tertiary structures that exhibit function, such as binding to a small molecule or catalyzing a chemical transformation. However, the biological application of these materials faces a great challenge because the host cells can detect and destroy exogenous nucleic acids. We are interested in finding solutions to this major problem and develop new materials with more catalytic activity and higher nuclease-resistance.
Enhanced Nonenzymatic RNA Copying with 2-Aminoimidazole-Activated Nucleotides. Li, L., Prywes, N., Tam, C. P., O’Flaherty, D. K., Lelyveld, V. S., Izgu, E. C., Pal, A., and Szostak, J. W. J. Am. Chem. Soc. 2017, 139, 1810–1813.
Downstream Oligonucleotides Strongly Enhance the Affinity of GMP to RNA Primer-Template Complexes.Tam, C. P., Fahrenbach, A. C., Björkbom, A., Prywes, N., Izgu, E. C., and Szostak, J. W. J. Am. Chem. Soc. 2017, 139, 571–574.
N-Carboxyanhydride-Mediated Fatty Acylation of Amino Acids and Peptides for Functionalization of the Protocell Membrane. Izgu, E. C., Björkbom, A., Kamat, N. P., Lelyveld, V. S., Zhang, W., Jia, T. Z., and Szostak, J. W. J. Am. Chem. Soc. 2016, 138, 16669–16676
Synthesis of Activated 3′-Amino-3′-deoxy-2-thio-thymidine, a Superior Substrate for the Nonenzymatic Copying of Nucleic Acid Templates. Izgu, E. C., Oh, S. S. and Szostak, J. W. Chem. Commun. 2016, 52, 3684–3686.
Uncovering the Thermodynamics of Monomer Binding for RNA Replication. Izgu, E. C.,* Fahrenbach, A. C.,* Zhang, N., Li L., Zhang, W.; Blain, C., Larsen, A. T., and Szostak, J. W. J. Am. Chem. Soc. 2015, 137, 6373–6382.
Total Synthesis of (±)-Leuconolam: Intramolecular Allylic Silane Addition to a Maleimide Carbonyl Group. Izgu, E. C., and Hoye, T. R. Chem. Sci. 2013, 4, 2262–2266.
o-(Trialkylstannyl)anilines and Their Utility in Migita–Kosugi–Stille Cross-Coupling: Direct Introduction of the 2-Aminophenyl Substituent. Izgu, E. C., and Hoye, T. R. Tetrahedron Lett. 2012, 53, 4938–4941.
Access to Functionalized Steroid Side Chains via Modified Julia Olefination. Izgu, E. C., Burns, A. C., and Hoye, T. R. Org. Lett. 2011, 13, 703–705.
Long-range Shielding Effects in the H NMR Spectra of Mosher-like Ester Derivatives. Hoye, T. R., Erickson, S. E., Erickson-Birkedahl, S. L., Hale, C. R. H., Izgu, E. C., Mayer, M. J., Notz, P. K., and Renner, M. K. Org. Lett. 2010, 12, 1768–1771.
Catalytic Enantioselective Addition of Diethylzinc to Aldehydes Using Aziridine Based Chiral Ligands. Bulut, A., Aslan, A., Izgu, E. C., and Dogan, O. Tetrahedron: Asymm. 2007, 18, 1013–1016.