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.
Selected References
"Introducing metallocene into a triazole peptide conjugate reduces its off-rate and enhances its affinity and antiviral potency for HIV-1 gp120"
Gopi, H., Cocklin, S., Pirrone, V., McFadden, K., Tuzer, F., Zentner, I., Ajith, S., Baxter, S., Jawanda, N., Krebs, F., Chaiken, I.
Journal of Molecular Recognition 22: 169-174, 2009.
"Isotropic display of biomolecules on CNT arrayed nanostructures"
Contarino, M., Withey, G., Chaiken, I.
In: Biosensing Using Nanomaterials. Arben Merkoci, editor. Wiley Interscience, 2009. pp. 39-65.
"Structural determinants for affinity enhancement of a dual antagonist peptide entry inhibitor of HIV-1 envelope gp120"
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.
Journal of Medicinal Chemistry 51: 2638-47, 2008.
"Structure-based rationale for Interleukin 5 receptor antagonism"
Ishino, T., Harrington, A., Gopi, H. and Chaiken, I.
Current Pharmaceutical Design 14: 1231-9, 2008.
"Slow-dissociation effect of common signaling subunit beta on IL5 and GM-CSF receptor assembly"
Ishino, T., Harrington, A., Zaks-Zilberman, M., Scibek, J., and Chaiken, I.
Cytokine 42: 179-90, 2008.
"Interleukin-5 receptor subunit oligomerization and rearrangement revealed by fluorescence resonance energy transfer imaging"
Zaks-Zilberman, M., Harrington, A., Ishino, T. and Chaiken, I.
Journal of Biological Chemistry 283: 13398-406, 2008.
"Enhanced EGFR inhibition and distinct epitope recognition by EGFR antagonistic MABS C225 and 425"
Kamat, V., Donaldson, J., Kari, C., Quadros, M., Lelkes, P., Chaiken, I., Cocklin, S., Williams, J., Papazoglou, E. and Rodeck Ulrich.
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.
"HIV envelope binding by macrophage-expressed gp340 promotes HIV-1 infection"
Cannon, G., Yi, Y., Ni, H., Stoddard, E., Scales, D.A., Van Ryk, D.I., Chaiken, I., Malamud, D, and Weissman, D.
Journal of Immunology 181: 2065-2070, 2008.
"Recruitment pharmacophore for Interleukin 5 receptor alpha antagonism"
Bhattacharya, M., Pillalamari, U., Sarkhel, S., Ishino, T., Urbina, C., Jamerson, B., and Chaiken, I.
Biopolymers Peptide Science 88: 83-93, 2007.
"Machines and networks: protein recognition in biology"
McCourt, P., Nickels, J., Ishino, T., and Chaiken, I.
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.
"Broad-spectrum anti-HIV potential of a peptide HIV-1 entry inhibitor"
Cocklin S., Gopi, H., Querido B., Nimmagadda, D., Kuriakose, S., Cicala, C., Ajith, S., Baxter, S., Arthos, J., Martin-Garcia, J., and Chaiken, I.
Journal of Virology 81: 3645-8, 2007.
"Click chemistry on azidoproline: high-affinity dual antagonist for HIV-1 envelope glycoprotein gp120"
Gopi, H. N., Tirupula K.C., Baxter, S., Ajith, S. and Chaiken, I.M.
ChemMedChem 1: 54-57, 2006.
"Asymmetric usage of antagonist charged residues derives interleukin-5 receptor recruitment but is insufficient for receptor activation"
Ishino, T., Pillalamarri, U., Panarello, D., Bhattacharya, M., Urbina, C., Horvat, S., Sarkhel. S., Jameson, B. and Chaiken I.
Biochemistry 45: 1106-1115, 2006.
"Real-time monitoring of the membrane-binding and insertion properties of the cholesterol-dependent cytolysin anthrolysin O from Bacillus anthracis"
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.
Journal of Molecular Recognition 19: 354-62, 2006.
"Modular, self-assembling peptide linkers for stable and regenerable carbon nanotube biosensor interfaces"
Contarino, M., Sergi, M., Harrington, A., Lazareck, A., Xu, J., Chaiken, I.M.
Journal of Molecular Recognition 19: 363-371, 2006.
"Antibody binding in proximity to retroviral envelope glycoproteins leads to a basal level of neutralization"
Yang, X., Lipchina, I., Cocklin, S., Chaiken, I. and Sodroski, J.
Journal of Virology, 80: 11404-8, 2006.
"Receptor epitope usage by interleukin 5 mimetic peptide"
Ishino T, Urbina C, Bhattacharya M, Panarello D and Chaiken I.
Journal of Biological Chemistry 280: 22951 22961, 2005.
"Advancement and utilization of biosensors for protein interaction analysis and proteomics"
Cocklin, S., Ishino, T., Sergi, M., Nedelkov, D., Nelson, R., and Chaiken, I.
In: Protein-Protein Interactions: A Molecular Cloning Manual. E. Golemis and P. Adams, eds., Cold Spring Harbor Press, Cold Spring Harbor, NY, 377-398, 2005.
"Interaction with CD4 and antibodies to CD4-induced epitopes of monomeric gp120 from a microglia-adapted human immunodeficiency virus type 1 isolate"
Martín-García J., Cocklin S., Chaiken I.M., and González-Scarano F.
Journal of Virology 79: 6703-6713, 2005.
"Cytokine recognition of human IL5 receptor"
Ishino T, Robertson N and Chaiken I.
In: Vitamins and Hormones (Litwack, G., ed) 71: 321-344, Academic Press, NY, 2005.
"Mode of action for linear peptide inhibitors of HIV-1 gp120 interactions"
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.
Biochemistry 43: 1928-1938, 2004.
"Kinetic interaction analysis of human interleukin 5 receptor α mutants reveals a unique binding topology and charge distribution for cytokine recognition"
Ishino T, Pasut G, Scibek J, and Chaiken I.
Journal of Biological Chemistry 279: 9547-9556, 2004.
"Cyclic peptide interleukin 5 antagonists mimic CD turn recognition epitope for receptor α"
Ruchala, P., Varadi, G., Ishino, T., Scibek, J., Bhattacharya, M., Urbina, C., Van Ryk, D., Uings, I., and Chaiken, I.
Biopolymers 73: 556-568, 2004.
"Proteins, recognition networks and developing interfaces for macromolecular biosensing"
Sergi, M., Zurawski, J., Cocklin, S., and Chaiken, I.
Journal of Molecular Recognition 17: 198-208, 2004.
"Small-molecule inhibitors of HIV-1 entry block receptor-induced conformational changes in the viral envelope glycoproteins"
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.
Proceedings of the National Academy of Science U.S.A., 101: 5036-4, 2004.
"Biosensor analysis of receptor-ligand interactions"
Wu, S.-J., and Chaiken, I.
Methods in Molecular Biology 249: 93-110, 2004.
"Interactions of HIV-1 proteins gp120 and Nef with cellular partners define a novel allosteric paradigm"
Leavitt, S. A., Schön, A., Klein, J. C., Manjappara, U., Chaiken, I. M. and Freire, E.
Current Protein and Peptide Science, 5: 1-8, 2004.
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