Image of Chaiken, Irwin

Irwin Chaiken, Ph.D.

Professor

  • Department:Biochemistry & Molecular Biology
  • Education: PhD, Biological Chemistry, University of California at Los Angeles (1968)
Research Overview

Research Interests: Protein interaction mechanisms and antagonism; HIV-1 cell entry

Lab: Chaiken Lab

Research

Our research program is centered on molecular and structural mechanisms of protein recognition and antagonism. The major current focus is on the protein machine that controls 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 and biophysical tools.  We use envelope protein structure and mechanism as a basis for deriving peptidomimetic inactivators of HIV-1 and to determine their molecular and virological modes of action.  Env inhibitors being discovered in this work are being evaluated for use in the development of AIDS therapeutics, microbicides and vaccines.  In addition, we seek to stimulate cross-disciplinary research and education programs to reveal fundamental nanoscale mechanisms of protein machines at membrane surfaces and in cells.

Collaborating for Culturally-Competent Care
Professors Jeffrey Jacobson, Jill Foster, Brian Wigdahl and Irwin Chaiken give valuable insight into the pivotal collaborative work they are performing in the ongoing battle against HIV/AIDS. Download PDF File

In the News

Publications

Selected References

"Solid-State Nanopore Detection of Protein Complexes; Applications in Healthcare and Protein Kinetics."
Freedman KJ, Bastian AR, Chaiken I, and Kim MJ
Small 2012, in press.

"Non-Natural Peptide Triazole Antagonists of HIV-1 Envelope gp120."
Kamanna K, Aneja R, Duffy C, Kubinski P, Rodrigo Moreira D, Bailey LD, McFadden K, Schӧn A, Holmes A, Tuzer F, Contarino M, Freire E, Chaiken IM 
ChemMedChem 2012, in press.

"HIV-1 Env gp120 Structural Determinants for Peptide Triazole Dual Receptor Site Antagonism."
Tuzer F, Madani M, Kantharaju, Zentner I, LaLonde J, Holmes A, Upton E, Rajagopal S,McFadden K, Contarino M, Sodroski, Chaiken
Proteins: Structure, Function, and Bioinformatics 2012, In press. 

"Antiviral Breadth and Combination Potential of Peptide Triazole HIV-1 Entry Inhibitors. "
McFadden K, Fletcher P, Rossi F, Kantharaju, Umashankara M, Pirrone V, Rajagopal S, Gopi H, Krebs FC, Martin-Garcia J, Shattock, RJ, Chaiken I
Antimicrob Agents Chemother. 56(2): 1073-80 2012

"Multivalent and Flexible PEG-Nitrilotriacetic Acid Derivatives for Non-covalent Protein Pegylation."
Mero A, Ishino T, Chaiken I, Veronese FM, Pasut G.
Pharm Res. 2011 Oct;28(10):2412-21. Epub May 25 2011

"A Protein Engineering Approach Differentiates the Functional Importance of Carbohydrate Moieties of Interleukin-5 Receptor α."
Ishino T, Economou NJ, McFadden K, Zaks-Zilberman M, Jost M, Baxter S, Contarino MR, Harrington AE, Loll PJ, Pasut G, Lievens S, Tavernier J, Chaiken I.
Biochemistry. 2011 Sep  6;50(35):7546-56. Epub Aug 10 2011

"Cell Free HIV-1 Virucidal Action by Modified Peptide Triazole Inhibitors of Env gp120."
Bastian RA, Kantharaju, McFadden K, Duffy C, Rajagopal S, Contarino M, Papazoglou E, Chaiken I
ChemMedChem. 6: 1-5, 2011.

"Monoclonal Antibody m18 Epitopes Leading to Dual Receptor Antagonism of HIV-1 gp120."
Gift SK, McFadden K, Zentner IJ, Rajagopal S, Zhang MY, Dimitrov DS, Chaiken I
Biochemistry. 50: 2769–2779, 2011.

"Conformational and Structural Features of HIV-1 gp120 Underlying Dual Receptor Antagonism by the Cross-Reactive Neutralizing Antibody m18."
Gift S. K., Zentner I., Schon A., McFadden K., UmaShankara M, Rajagopal S., Contarino, M.; Duffy, C.; Courter, J. R.; Zhang, M. Y.; Gershoni, J.; Cocklin S, Dimitrov DS, Smith AB III, Freire E, Chaiken I 
Biochemistry. 50: 2756–2768, 2011.

The Active Core in a Triazole Peptide Dual-Site Antagonist of HIV-1 gp120.
Umashankara M, McFadden K, Zentner I, Schön A, Rajagopal S, Tuzer F, Kuriakose SA, Contarino M, Lalonde J, Freire E, Chaiken I 
ChemMedChem 2010

"Use of the quartz crystal microbalance to monitor ligand-induced conformational rearrangements in HIV-1 envelope protein gp120."
Lee HS, Contarino M, Umashankara M, Schon A, Freire E, Smith AB, Chaiken IM and Penn LS 
Analytical and Bioanalytical Chemistry. Volume 396, Number 3, 1143-1152.  2010.

"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.

"A recombinant allosteric lectin antagonist of HIV-1 envelope gp120 interactions"
McFadden K, Cocklin S, Gopi HN, Baxter S, Ajith S, Mahmood N, Shattock R, Chaiken I
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 DA, Van Ryk DI, 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 HN, Tirupula KC, Baxter S, Ajith S and Chaiken IM
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 NM, Weeks SD, Weber H-W, Young E, Seal S, Zhang C, Mosser E, Loll PJ, Saunders AJ, Rest R, and Chaiken IM
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 IM
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 IM, 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 AC, 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 JM, Chruma JJ, Klein JC, Schon A., Phan N, Wang L, Biorn AB, Cocklin S, Chaiken I, Freire E, Smith AB, and Sodroski JG
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 SA, Schön A, Klein JC, Manjappara U, Chaiken IM and  Freire E
Current Protein and Peptide Science, 5: 1-8, 2004.

Academic Location

Department of Biochemistry & Molecular Biology
245 North 15th Street
Mail Stop 497
Philadelphia, PA 19102
Phone: 215-762-4197
Fax: 215-762-4452

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