Utilization of I-domain of LFA-1 to target drug and marker molecules to Leukocytes.
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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English English |
| Published: |
Ivyspring International Publisher
2011
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| Online Access: | http://psasir.upm.edu.my/id/eprint/25114/ http://psasir.upm.edu.my/id/eprint/25114/1/Utilization%20of%20I.pdf |
| _version_ | 1848845220586717184 |
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| author | Manikwar, Prakash Tejo, Bimo Ario Shinogle, Heather Moore, David S. Zimmerman, Tahl Blanco, Francisco Siahaan, Teruna J. |
| author_facet | Manikwar, Prakash Tejo, Bimo Ario Shinogle, Heather Moore, David S. Zimmerman, Tahl Blanco, Francisco Siahaan, Teruna J. |
| author_sort | Manikwar, Prakash |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-15T08:43:21Z |
| format | Article |
| id | upm-25114 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English English |
| last_indexed | 2025-11-15T08:43:21Z |
| publishDate | 2011 |
| publisher | Ivyspring International Publisher |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-251142015-10-20T05:55:48Z http://psasir.upm.edu.my/id/eprint/25114/ Utilization of I-domain of LFA-1 to target drug and marker molecules to Leukocytes. Manikwar, Prakash Tejo, Bimo Ario Shinogle, Heather Moore, David S. Zimmerman, Tahl Blanco, Francisco Siahaan, Teruna J. 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. Ivyspring International Publisher 2011 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/25114/1/Utilization%20of%20I.pdf Manikwar, Prakash and Tejo, Bimo Ario and Shinogle, Heather and Moore, David S. and Zimmerman, Tahl and Blanco, Francisco and Siahaan, Teruna J. (2011) Utilization of I-domain of LFA-1 to target drug and marker molecules to Leukocytes. Theranostics, 1 (1). pp. 277-289. ISSN 1838-7640 http://ivyspring.com/ English |
| spellingShingle | Manikwar, Prakash Tejo, Bimo Ario Shinogle, Heather Moore, David S. Zimmerman, Tahl Blanco, Francisco Siahaan, Teruna J. Utilization of I-domain of LFA-1 to target drug and marker molecules to Leukocytes. |
| title | Utilization of I-domain of LFA-1 to target drug and marker molecules to Leukocytes. |
| title_full | Utilization of I-domain of LFA-1 to target drug and marker molecules to Leukocytes. |
| title_fullStr | Utilization of I-domain of LFA-1 to target drug and marker molecules to Leukocytes. |
| title_full_unstemmed | Utilization of I-domain of LFA-1 to target drug and marker molecules to Leukocytes. |
| title_short | Utilization of I-domain of LFA-1 to target drug and marker molecules to Leukocytes. |
| title_sort | utilization of i-domain of lfa-1 to target drug and marker molecules to leukocytes. |
| url | http://psasir.upm.edu.my/id/eprint/25114/ http://psasir.upm.edu.my/id/eprint/25114/ http://psasir.upm.edu.my/id/eprint/25114/1/Utilization%20of%20I.pdf |