Cover Image

Effect of modification of the physicochemical properties of ICAM-1-derived peptides on internalization and intracellular distribution in the human leukemic cell line HL-60

The objective of this work is to test the hypothesis that increasing the hydrophilicity of DOX−peptide conjugates may modify their entry mechanisms into HL-60 cells from passive diffusion to receptor-mediated uptake. To test this hypothesis, the entry mechanisms and the intracellular disposition of...

Full description

Saved in:
Bibliographic Details
Main Authors: Majumdar, Sumit, Tejo, Bimo Ario, Badawi, Ahmed H., Moore, David, Krise, Jeffrey P., Siahaan, Teruna J.
Format: Article
Language:English
Published: American Chemical Society 2009
Online Access:http://psasir.upm.edu.my/id/eprint/14272/1/Effect%20of%20modification%20of%20the%20physicochemical%20properties%20of%20ICAM.pdf
http://psasir.upm.edu.my/id/eprint/14272/
Tags: Add Tag
No Tags, Be the first to tag this record!
id my.upm.eprints.14272
record_format eprints
spelling my.upm.eprints.142722015-10-22T06:46:57Z http://psasir.upm.edu.my/id/eprint/14272/ Effect of modification of the physicochemical properties of ICAM-1-derived peptides on internalization and intracellular distribution in the human leukemic cell line HL-60 Majumdar, Sumit Tejo, Bimo Ario Badawi, Ahmed H. Moore, David Krise, Jeffrey P. Siahaan, Teruna J. The objective of this work is to test the hypothesis that increasing the hydrophilicity of DOX−peptide conjugates may modify their entry mechanisms into HL-60 cells from passive diffusion to receptor-mediated uptake. To test this hypothesis, the entry mechanisms and the intracellular disposition of DOX−cIBR7, DOX−PEGcIBR7, FITC−cIBR, and FITC−cIBR7 were evaluated in HL-60 cells. To increase the hydrophilicity of the peptide, the cIBR peptide (cyclo(1,12)PenPRGGSVLVTGC) was modified to cIBR7 peptide (cyclo(1,8)CPRGGSVC) by removing the hydrophobic residues at the C-terminus. DOX−cIBR7 conjugate, which has higher hydrophilicity than DOX−cIBR, was synthesized. Second, a hydrophilic linker (11-amino-3,6,9-trioxaundecanate linker) was incorporated between DOX and cIBR7 to generate DOX−PEGcIBR7 with higher hydrophilicity than DOX−cIBR7. As controls, FITC−cIBR and FITC−cIBR7 were used to check for any endocytic uptake process of the peptide. As previously found with DOX−cIBR, DOX−cIBR7, and DOX−PEGcIBR7, conjugates enter the cells via passive diffusion and not via the energy-dependent endocytic process. This result suggests that an increase in hydrophilicity does not influence the entry mechanism of the DOX−peptide conjugates. In contrast to the DOX−cIBR7 conjugate, the FITC−cIBR7 conjugate showed energy-dependent cellular entry into the cells and followed an endocytic pathway similar to that for dextran. Finally, the entry of DOX−cIBR7 and DOX−PEGcIBR into the cell cytosol was shown to be due to the properties of DOX and not to those of the peptide. American Chemical Society 2009 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/14272/1/Effect%20of%20modification%20of%20the%20physicochemical%20properties%20of%20ICAM.pdf Majumdar, Sumit and Tejo, Bimo Ario and Badawi, Ahmed H. and Moore, David and Krise, Jeffrey P. and Siahaan, Teruna J. (2009) Effect of modification of the physicochemical properties of ICAM-1-derived peptides on internalization and intracellular distribution in the human leukemic cell line HL-60. Molecular Pharmaceutics, 6 (2). pp. 396-406. ISSN 1543-8384; ESSN: 1543-8392 10.1021/mp800120t
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
description The objective of this work is to test the hypothesis that increasing the hydrophilicity of DOX−peptide conjugates may modify their entry mechanisms into HL-60 cells from passive diffusion to receptor-mediated uptake. To test this hypothesis, the entry mechanisms and the intracellular disposition of DOX−cIBR7, DOX−PEGcIBR7, FITC−cIBR, and FITC−cIBR7 were evaluated in HL-60 cells. To increase the hydrophilicity of the peptide, the cIBR peptide (cyclo(1,12)PenPRGGSVLVTGC) was modified to cIBR7 peptide (cyclo(1,8)CPRGGSVC) by removing the hydrophobic residues at the C-terminus. DOX−cIBR7 conjugate, which has higher hydrophilicity than DOX−cIBR, was synthesized. Second, a hydrophilic linker (11-amino-3,6,9-trioxaundecanate linker) was incorporated between DOX and cIBR7 to generate DOX−PEGcIBR7 with higher hydrophilicity than DOX−cIBR7. As controls, FITC−cIBR and FITC−cIBR7 were used to check for any endocytic uptake process of the peptide. As previously found with DOX−cIBR, DOX−cIBR7, and DOX−PEGcIBR7, conjugates enter the cells via passive diffusion and not via the energy-dependent endocytic process. This result suggests that an increase in hydrophilicity does not influence the entry mechanism of the DOX−peptide conjugates. In contrast to the DOX−cIBR7 conjugate, the FITC−cIBR7 conjugate showed energy-dependent cellular entry into the cells and followed an endocytic pathway similar to that for dextran. Finally, the entry of DOX−cIBR7 and DOX−PEGcIBR into the cell cytosol was shown to be due to the properties of DOX and not to those of the peptide.
format Article
author Majumdar, Sumit
Tejo, Bimo Ario
Badawi, Ahmed H.
Moore, David
Krise, Jeffrey P.
Siahaan, Teruna J.
spellingShingle Majumdar, Sumit
Tejo, Bimo Ario
Badawi, Ahmed H.
Moore, David
Krise, Jeffrey P.
Siahaan, Teruna J.
Effect of modification of the physicochemical properties of ICAM-1-derived peptides on internalization and intracellular distribution in the human leukemic cell line HL-60
author_facet Majumdar, Sumit
Tejo, Bimo Ario
Badawi, Ahmed H.
Moore, David
Krise, Jeffrey P.
Siahaan, Teruna J.
author_sort Majumdar, Sumit
title Effect of modification of the physicochemical properties of ICAM-1-derived peptides on internalization and intracellular distribution in the human leukemic cell line HL-60
title_short Effect of modification of the physicochemical properties of ICAM-1-derived peptides on internalization and intracellular distribution in the human leukemic cell line HL-60
title_full Effect of modification of the physicochemical properties of ICAM-1-derived peptides on internalization and intracellular distribution in the human leukemic cell line HL-60
title_fullStr Effect of modification of the physicochemical properties of ICAM-1-derived peptides on internalization and intracellular distribution in the human leukemic cell line HL-60
title_full_unstemmed Effect of modification of the physicochemical properties of ICAM-1-derived peptides on internalization and intracellular distribution in the human leukemic cell line HL-60
title_sort effect of modification of the physicochemical properties of icam-1-derived peptides on internalization and intracellular distribution in the human leukemic cell line hl-60
publisher American Chemical Society
publishDate 2009
url http://psasir.upm.edu.my/id/eprint/14272/1/Effect%20of%20modification%20of%20the%20physicochemical%20properties%20of%20ICAM.pdf
http://psasir.upm.edu.my/id/eprint/14272/
_version_ 1643825583254142976
score 13.211869

Similar Items