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Theranostics 2011; 1:277-289. doi:10.7150/thno/v01p0277 This volume Cite

Research Paper

Utilization of I-domain of LFA-1 to Target Drug and Marker Molecules to Leukocytes

Prakash Manikwar1, Bimo A. Tejo1,2, Heather Shinogle3, David S. Moore3, Tahl Zimmerman4, Francisco Blanco4,5, Teruna J. Siahaan1, ✉

1. Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047, USA
2. Current Address: Department of Chemistry, Universiti Putra, Malaysia, 43400 UPM Serdang, Selangor, Malaysia
3. Microscopy and Imaging Laboratory, University of Kansas, Lawrence, KS 66045, USA
4. Unidad de Biología Estructural, CIC bioGUNE, 48160 Derio, Bizkaia, Spain
5. IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain

✉ Corresponding author: Dr. Teruna J. Siahaan, Department of Pharmaceutical Chemistry, The University of Kansas, Simons Research Laboratories, 2095 Constant Avenue, Lawrence, KS 66047, USA. Tel.: (785) 864-7327; Fax: (785) 864-5736; E-mail: siahaanedu More

Citation:
Manikwar P, Tejo BA, Shinogle H, Moore DS, Zimmerman T, Blanco F, Siahaan TJ. Utilization of I-domain of LFA-1 to Target Drug and Marker Molecules to Leukocytes. Theranostics 2011; 1:277-289. doi:10.7150/thno/v01p0277. https://www.thno.org/v01p0277.htm
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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.

Keywords: ICAM-1, FITC-I-domain, binding, endocytosis, Raji cells

Citation styles

APA
Manikwar, P., Tejo, B.A., Shinogle, H., Moore, D.S., Zimmerman, T., Blanco, F., Siahaan, T.J. (2011). Utilization of I-domain of LFA-1 to Target Drug and Marker Molecules to Leukocytes. Theranostics, 1, 277-289. https://doi.org/10.7150/thno/v01p0277.

ACS
Manikwar, P.; Tejo, B.A.; Shinogle, H.; Moore, D.S.; Zimmerman, T.; Blanco, F.; Siahaan, T.J. Utilization of I-domain of LFA-1 to Target Drug and Marker Molecules to Leukocytes. Theranostics 2011, 1, 277-289. DOI: 10.7150/thno/v01p0277.

NLM
Manikwar P, Tejo BA, Shinogle H, Moore DS, Zimmerman T, Blanco F, Siahaan TJ. Utilization of I-domain of LFA-1 to Target Drug and Marker Molecules to Leukocytes. Theranostics 2011; 1:277-289. doi:10.7150/thno/v01p0277. https://www.thno.org/v01p0277.htm

CSE
Manikwar P, Tejo BA, Shinogle H, Moore DS, Zimmerman T, Blanco F, Siahaan TJ. 2011. Utilization of I-domain of LFA-1 to Target Drug and Marker Molecules to Leukocytes. Theranostics. 1:277-289.

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