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Antigen-specific blocking of immunological synapse formation using bifunctional peptide, Utilization of I-domain of LFA-1 to Target Drug and Marker Molecules to Leukocytes
Manikwar, Prakash Tejo, Bimo A. Shinogle, Heather E. Moore, David S. Zimmerman, Tahl Blanco, Francisco Siahaan, Teruna J.
Manikwar, Prakash
Tejo, Bimo A.
Shinogle, Heather E.
Moore, David S.
Zimmerman, Tahl
Blanco, Francisco
Siahaan, Teruna J.
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Abstract
The long-term objective of this project is to utilize the I-domain protein for the alpha-subunit of LFA-1 to target drugs to lymphocytes by binding to ICAM receptors on the cell surface. The short-term goal is to provide proof-of-concept that I-domain conjugated to small molecules can still bind to and uptake by ICAM-1 on the surface of lymphocytes (i.e., Raji cells). To accomplish this goal, the I-domain protein was labeled with FITC at several lysine residues to produce the FITC-I-domain and CD spectroscopy showed that the FITC-I-domain has a secondary structure similar to that of the parent I-domain. The FITC-I-domain was taken up by Raji cells via receptor-mediated endocytosis and its uptake can be blocked by anti-I-domain mAb but not by its isotype control. Antibodies to ICAM-1 enhance the binding of I-domain to ICAM-1, suggesting it binds to ICAM-1 at different sites than the antibodies. The results in-dicate that fluorophore modification does not alter the binding and uptake properties of the I-domain protein. Thus, I-domain could be useful as a carrier of drug to target ICAM-1-expressing lymphocytes.
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This is the publisher's version.
Date
2011-05-01
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Publisher
Ivyspring International Publisher
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Keywords
Icam-1, Fitc-i-domain, Binding, Endocytosis, Raji cells
Citation
P. Manikwar, B.A. Tejo, H. Shinogle, D.S. Moore, T. Zimmerman, F.J. Blanco, and T.J. Siahaan, “Utilization of I-domain of LFA-1 to Target Drug and Marker Molecules to Leukocytes,” Theranostics. 1, 277–289 (2011).