Isaac Carrico, Associate Professor
B.S. University of California, Santa Barbara, 1997
Ph.D. California Institute of Technology, 2003
NIH Postdoctoral Fellowship, University of California, Berkeley, 2003-2006
Phone: (631) 632-7935
Chemical Biology, Bioorganic Chemistry and Protein Engineering
The research in our group centers around the concept of chemical biology. In paticular, we introduce unnatural monomers into the biopolymers of life (proteins, oligosaccharides, oligonucleotides) for the purpose of tracking or perturbing biological processes. Methodologies that we rely upon include organic synthesis, biochemistry and molecular biology.
Metabolic engineering, in the context of our work, involves the introduction of unnatural functionality into biosynthetic processes. This results in the production of proteins, oligosaccharides and DNA with inherent unnatural functionality that can be used for tracking, dynamics studies, and subsequent chemical modification. One of our focuses within metabolic engineering is to use this technique to remodel the surfaces of eukaryotic viruses, which has been limited by solely genetic approaches. Many of the basic science and therapeutic applications, such as gene therapy, oncolytic viruses, and live vaccines, have been hindered by the inability to sufficiently control surface interactions.
Protein pharmaceuticals represent a rapidly expanding section of the pharmaceutical industry, this has been exacerbated by recent specificity issues with more traditional drugs. However, protein-based drugs are faced with their own set of limitations, particularly introduction, lifetime and immunogenicity. We focus on diminishing interactions with proteases and the complement system by introduction of unnatural functionality into the protein backbone.
Bioorthogonal reaction development
Precise chemical modification within a physiological context is a key hurdle facing many biosciences. The overwhelming diversity of native functionality complicates specific modification. Additionally, the environment dictates 55 M water, neutral pH and 37°C. Realistically the target molecule will be in low abundance and the labeling molecule should also be to prevent background. Our lab is focusing on the development of fast, chemoselective reactions that create stable linkages under these conditions. Of particular interest to us are electrocyclic reactions aided by molecular recognition events.
Oum, H. Y.; Carrico, I. S.; (2011) Targeting adenovirus via chemoselective modification with affibodies. Bioconj. Chem. In Revision.
Oum, H. Y.; Carrico, I. S.; (2011) Click modification of adenoviruses allows interrogation of integrin selective gene delivery. ChemBiochem. Submitted.
Nagarajan, S.; Taskent-Sezgin, H.; Parul, D.; Carrico, I.; Raleigh, D.; Dyer, R.; (2011) Differential ordering of the protein backbone and side chains during protein folding revealed by site-specific recombinant infrared probes. JACS, In Press.
Banerjee, P. S.; Oum H. Y.; Carrico, I. S.: (2011) Dual functionalization of oncolytic adenoviral vectors allows targeting combination therapy. Bioorg. Med. Chem. Lett. 29, 4985-4988.
Banerjee, P. S.; Ostapachuk, P.; Hearing, P.; Carrico, I. S.; (2011) Unnatural amino acid incorporation allows chemoselective modification and subsequent targeting of hAd5. J. Virol., 85, 7546-7554.
Boyce, M.; Carrico, I. S.; Ganguli, A.; Yu, S.; Hangauer, M.; Hubbard, S. C.; Kohler, J. J.; Bertozzi, C. R. (2011) Metabolic crosstalk allows labeling of O-linked β-N-acetylglucosamine-modified proteins via the N-acetylgalactosamine salvage pathway. Proc. Nat. Acad. Sci., 108, 3141-3146.
Banerjee, P.S.; Carrico, I. S.; (2011) Chemoselective modification of viral proteins bearing metabolically introduced “clickable” amino acids and sugars. In Methods in Molecular Biology: Bioconjugation Protocols, 2nd ed., p. 55-67. Mark, S. S. ed. New York: Humana Press, 2011. (Invited Book Chapter)
Carrico, I. S.; Francis, M. B.; (2010) New frontiers in bioconjugation. Curr. Op. Chem. Biol. 14, 771-773.
Banerjee, P. S.; Ostapachuk, P.; Hearing, P.; Carrico, I. S.; (2010) Chemoselective
attachment of small molecule effector functionality to human adenoviruses facilitates
gene delivery to cancer cells. JACS, 132, 13615-13617.
Research Highlighted in ACS Chem. Biol. (2010) 5, 1005-1006.
Taskent-Sezgin, H.; Chung, J.; Banerjee, P. S.; Sureshbabu, N.; Dyer, R. B.; Carrico, I. S.; Raleigh, D. P.; (2010) Azidohomoalanine provides a conformationally sensitive IR probe of protein folding, protein structure and electrostatics which can be readily incorporated into proteins. Angew. Chem. Int. Eng. Ed. 49, 7473-7475.
Taskent-Sezgin, H.; Marek, P.; Thomas, R.; Goldberg, D.; Chung, J.; Carrico, I. S.; Raleigh, D. P. (2010) Modulation of p-cyanophenylalanine fluorescence by amino acid side chains and rational design of fluorescence probes of α-helix formation. Biochem. 49, 6290-6295.
Taskent-Sezgin, H.; Chung, J.; Patsalo, V.; Miyake-Stoner, S. J.; Miller, A. M.; Brewer, S. H.; Mehl, R. A.; Green, D. F.; Raleigh, D. P.; Carrico, I. S. (2009) Interpretation of p-Cyanophenylalanine Fluorescence in Proteins in Terms of Solvent Exposure and Contribution of Side-Chain Quenchers: A Combined Fluorescence, IR and Molecular Dynamics Study. Biochem. 48, 9040-9046.
Carrico, I. S.; Kirshenbaum, K. (2009) Designer labels for virus coats. Nat. Nano. 4, 14-15.
Carrico, I. S. (2008) A cysteine protease that cuts and pastes. Nat. Chem. Biol. 4, 525-526.
Carrico, I. S. (2008) Chemoselective protein modification: hitting the target. Chem. Soc. Rev. 37, 1423-1431.
Carrico, I. S.; Carlson, B.; Bertozzi, C. R. (2007) A genetically encodable aldehyde-tag for site-specific protein modification. Nat. Chem. Biol. 3, 321-322.
Laughlin, S. T.; Agard, N. A.; Baskin, J. M.; Carrico, I. S.; Chang, P. V.; Ganjuli, A. S.; Hangauer, M. J.; Lo, A.; Prescher, J. A.; Bertozzi, C. R. (2006) Metabolic labeling of glycans with azido sugars for visualization and glycoproteomics. Meth. Enz. 415, 230-250.
Carrico, I. S.; Maskarinec, S.A.; Heilshorn, S. A.; Mock, M. L.; Liu, J. C.; Nowatzky, P. J.; Franck, C.; Ravichandran, G.; Tirrell, D. A. (2007) Lithographic patterning of photoreactive cell-adhesive proteins. J. Am. Chem. Soc. 129, 4874-4875.
Datta, D.; Wang, P.; Carrico, I. S.; Mayo, S. L.; Tirrell, D. A. (2002) A designed phenylalanyl-tRNA synthetase variant allows efficient in vivo incorporation of aryl ketone functionality into proteins. J. Am. Chem. Soc. 124, 5652-5653.
Kirshenbaum, K.; Carrico, I. S.; Tirrell, D. A. (2002) Biosynthesis of proteins incorporating a versatile set of phenylalanine analogs. ChemBioChem. 3, 235-237.
Pierce, D.A.; Jotterand, N.; Carrico, I.S.; Imperiali, B. (2001) Derivatives of 8-hydroxy-2-methylquinoline are powerful prototypes for zinc sensors in biological systems. J. Am. Chem. Soc. 123, 5160-5161.
Lipshutz, B. H.; James, B.; Vance, S.; Carrico, I. S. (1997) A potentially general intramolecular biaryl coupling approach to optically pure 2,2’-BINOL analogs. Tet. Let. 38, 753-756.