Our research is centered on molecular and structural mechanisms of protein recognition and antagonism.
The major area of effort is on the protein-protein complexes that control HIV-1 cell entry into host cells. We investigate interactions of the viral envelope proteins with host cell receptor proteins using a multidisciplinary approach combining protein chemistry, molecular biology, peptidomimetic synthesis and biophysical tools. Molecular inhibitors being discovered in this work are being evaluated for use in the development of AIDS therapeutics, microbicides and vaccines. In coordination with the above research program, we pursue the development and application of emerging technologies to measure protein-protein interactions in solution and in cells as a means to identify mechanism-based and structure-based solutions to problems in health and disease.
Chaiken Lab
Selected References
Gopi, H., Cocklin, S., Pirrone, V., McFadden, K., Tuzer, F., Zentner, I., Ajith, S., Baxter, S., Jawanda, N., Krebs, F., Chaiken, I. Introducing metallocene into a triazole peptide conjugate reduces its off-rate and enhances its affinity and antiviral potency for HIV-1 gp120. Journal of Molecular Recognition 22: 169-174, 2009.
Contarino, M., Withey, G., Chaiken, I. Isotropic display of biomolecules on CNT arrayed nanostructures. In: Biosensing Using Nanomaterials. Arben Merkoci, editor. Wiley Interscience, 2009. pp. 39-65.
Gopi, H., Pirrone, V., LaLonde, J., Madani, N., Tuzer, F., Baxter, S., Zentner, I., Cocklin, S., Miller, S., Krebs, F., Sodroski, J. and Chaiken, I. Structural determinants for affinity enhancement of a dual antagonist peptide entry inhibitor of HIV-1 envelope gp120. Journal of Medicinal Chemistry 51: 2638-47, 2008.
Ishino, T., Harrington, A., Gopi, H. and Chaiken, I. Structure-based rationale for Interleukin 5 receptor antagonism. Current Pharmaceutical Design 14: 1231-9, 2008.
Ishino, T., Harrington, A., Zaks-Zilberman, M., Scibek, J., and Chaiken, I. Slow-dissociation effect of common signaling subunit beta on IL5 and GM-CSF receptor assembly. Cytokine 42: 179-90, 2008.
Zaks-Zilberman, M., Harrington, A., Ishino, T. and Chaiken, I. Interleukin-5 receptor subunit oligomerization and rearrangement revealed by fluorescence resonance energy transfer imaging. Journal of Biological Chemistry 283: 13398-406, 2008.
Kamat, V., Donaldson, J., Kari, C., Quadros, M., Lelkes, P., Chaiken, I., Cocklin, S., Williams, J., Papazoglou, E. and Rodeck Ulrich. Enhanced EGFR inhibition and distinct epitope recognition by EGFR antagonistic MABS C225 and 425. Cancer Biology and Therapy 7: 726-33, 2008.
McFadden, K., Cocklin, S., Gopi, H.N., Baxter, S., Ajith, S., Mahmood N., Shattock, R., Chaiken, I. (2007) A recombinant allosteric lectin antagonist of HIV-1 envelope gp120 interactions. Proteins: Structure, Function and Bioinformatics 67: 617-629, 2007.
Cannon, G., Yi, Y., Ni, H., Stoddard, E., Scales, D.A., Van Ryk, D.I., Chaiken, I., Malamud, D, and Weissman, D. HIV envelope binding by macrophage-expressed gp340 promotes HIV-1 infection. Journal of Immunology 181: 2065-2070, 2008.
Bhattacharya, M., Pillalamari, U., Sarkhel, S., Ishino, T., Urbina, C., Jamerson, B., and Chaiken, I. Recruitment pharmacophore for Interleukin 5 receptor alpha antagonism. Biopolymers Peptide Science 88: 83-93, 2007.
McCourt, P., Nickels, J., Ishino, T., and Chaiken, I. Machines and networks: protein recognition in biology. In: Handbook of Biosensors and Biochips, Marks, R.S., Lowe, C., Cullen, D.C., Weetall, H. and Karube, I., Eds., John Wiley and Sons, 2007, pp; 61-81.
Cocklin S., Gopi, H., Querido B., Nimmagadda, D., Kuriakose, S., Cicala, C., Ajith, S., Baxter, S., Arthos, J., Martin-Garcia, J., and Chaiken, I. Broad-spectrum anti-HIV potential of a peptide HIV-1 entry inhibitor. Journal of Virology 81: 3645-8, 2007.
Gopi, H. N., Tirupula K.C., Baxter, S., Ajith, S. and Chaiken, I.M. Click chemistry on azidoproline: high-affinity dual antagonist for HIV-1 envelope glycoprotein gp120. ChemMedChem 1: 54-57, 2006.
Ishino, T., Pillalamarri, U., Panarello, D., Bhattacharya, M., Urbina, C., Horvat, S., Sarkhel. S., Jameson, B. and Chaiken I. Asymmetric usage of antagonist charged residues derives interleukin-5 receptor recruitment but is insufficient for receptor activation. Biochemistry 45: 1106-1115, 2006.
Cocklin, S., Jost, M., Robertson, N.M., Weeks, S.D., Weber, H-W., Young, E., Seal, S., Zhang, C., Mosser, E., Loll, P.J., Saunders, A.J., Rest, R., and Chaiken, I. M. Real-time monitoring of the membrane-binding and insertion properties of the cholesterol-dependent cytolysin anthrolysin O from Bacillus anthracis. Journal of Molecular Recognition 19: 354-62, 2006.
Contarino, M., Sergi, M., Harrington, A., Lazareck, A., Xu, J., Chaiken, I.M. Modular, self-assembling peptide linkers for stable and regenerable carbon nanotube biosensor interfaces. Journal of Molecular Recognition 19: 363-371, 2006.
Yang, X., Lipchina, I., Cocklin, S., Chaiken, I. and Sodroski, J. Antibody binding in proximity to retroviral envelope glycoproteins leads to a basal level of neutralization. Journal of Virology, 80: 11404-8, 2006.
Ishino T, Urbina C, Bhattacharya M, Panarello D and Chaiken I. Receptor epitope usage by interleukin 5 mimetic peptide. Journal of Biological Chemistry 280: 22951 22961, 2005.
Cocklin, S., Ishino, T., Sergi, M., Nedelkov, D., Nelson, R., and Chaiken, I. Advancement and utilization of biosensors for protein interaction analysis and proteomics. Cold Spring Harbor, Protein-Protein Interactions: A Molecular Cloning Manual. E. Golemis and P. Adams, eds., Cold Spring Harbor Press, Cold Spring Harbor, NY, 377-398, 2005.
Martín-García J., Cocklin S., Chaiken I.M., and González-Scarano F. Interaction with CD4 and antibodies to CD4-induced epitopes of monomeric gp120 from a microglia-adapted human immunodeficiency virus type 1 isolate. Journal of Virology 79: 6703-6713, 2005.
Ishino T, Robertson N and Chaiken I. Cytokine recognition of human IL5 receptor. In Vitamins and Hormones (Litwack, G., ed) 71: 321-344, Academic Press, NY, 2005.
Biorn A C, Cocklin S, Madani N, Si Z, Ivanovic T, Samanen| J, Van Ryk DI, Pantophlet R, Burton DR, Freire E, Sodroski J, and Chaiken I. Mode of action for linear peptide inhibitors of HIV-1 gp120 interactions. Biochemistry 43: 1928-1938, 2004.
Ishino T, Pasut G, Scibek J, and Chaiken I. Kinetic interaction analysis of human interleukin 5 receptor α mutants reveals a unique binding topology and charge distribution for cytokine recognition. Journal of Biological Chemistry 279: 9547-9556, 2004.
Ruchala, P., Varadi, G., Ishino, T., Scibek, J., Bhattacharya, M., Urbina, C., Van Ryk, D., Uings, I., and Chaiken, I. Cyclic peptide interleukin 5 antagonists mimic CD turn recognition epitope for receptor α. Biopolymers 73: 556-568, 2004.
Sergi, M., Zurawski, J., Cocklin, S., and Chaiken, I. Proteins, recognition networks and developing interfaces for macromolecular biosensing. Journal of Molecular Recognition 17: 198-208, 2004.
Si, Z., Madani, N., Cox, J.M., Chruma, J.J., Klein, J.C., Schon, A., Phan, N., Wang, L., Biorn, A.B., Cocklin., S., Chaiken, I., Freire, E., Smith A.B., and Sodroski, J.G. Small-molecule inhibitors of HIV-1 entry block receptor-induced conformational changes in the viral envelope glycoproteins. Proceedings of the National Academy of Science U.S.A., 101: 5036-4, 2004.
Wu, S.-J., and Chaiken, I. Biosensor analysis of receptor-ligand interactions. Methods in Molecular Biology 249: 93-110, 2004.
Leavitt, S. A., Schön, A., Klein, J. C., Manjappara, U., Chaiken, I. M. and Freire, E.. Interactions of HIV-1 proteins gp120 and Nef with cellular partners define a novel allosteric paradigm. Current Protein and Peptide Science, 5: 1-8, 2004. |