title: Utilization of I-domain of LFA-1 to Target Drug and Marker Molecules to Leukocytes.
abstract: The long-term objective of this project is to utilize the I-domain protein for the α-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 indicate 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.
authors: 1. Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047, USA.
authors: Prakash
authors: P
authors: Manikwar
authors: Bimo A
authors: BA
authors: Tejo
authors: Heather
authors: H
authors: Shinogle
authors: David S
authors: DS
authors: Moore
authors: Tahl
authors: T
authors: Zimmerman
authors: Francisco
authors: F
authors: Blanco
authors: Teruna J
authors: TJ
authors: Siahaan
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