@article {2396,
	title = {Binding and Uptake of RGD-Containing Ligands to Cellular alpha(v)beta(3) Integrins},
	journal = {International Journal of Peptide Research and Therapeutics},
	volume = {15},
	number = {1},
	year = {2009},
	note = {ISI Document Delivery No.: 430WTTimes Cited: 2Cited Reference Count: 34Cressman, Sonya Sun, Ying Maxwell, E. Jane Fang, Ning Chen, David D. Y. Cullis, Pieter R.},
	month = {Mar},
	pages = {49-59},
	type = {Article},
	abstract = {The cyclic peptide, cRGDf[N(me)]V, binds to the alpha(v)beta(3) integrin and can disrupt binding of the integrin to its natural ligands in the extracellular matrix. In this work, the ability of a water-soluble, fluorescently labeled variant of the RGD-containing peptide (cRGDfK-488) to bind to integrins on human umbilical vascular endothelial cells (HUVEC) and subsequently undergo endocytosis was characterized. This information was compared to the binding and uptake properties of an alpha(v)beta(3) integrin-specific monoclonal antibody, LM609X. The specificity of the RGD-containing peptide is assessed by comparison with control peptide that does not bind to the alpha(v)beta(3) integrin, cRADfK-488. Using a high purity construct, it is shown that the RGD ligand exhibits dissociation constants in the micromolar range whereas LM609X exhibits dissociation constants in the nanomolar range. However, the RGD ligand showed greater uptake following incubation at temperatures which permit endocytosis. A 7.4-fold increase in uptake of the RGD peptide was observed following a 1 h incubation with HUVEC at 37 degrees C (an endocytosis permissive temperature), as compared to that at 4 degrees C (an endocytosis prohibitive temperature). In contrast, only a 1.9-fold increase in cell-associated fluorescence was observed for similar incubations with LM609X. Results from fluorescence microscopy supports the notion that the RGD peptide is rapidly endocytosed at 37 degrees C as compared to LM609X. These results are discussed with regard to previous work indicating that RGD ligands enter cells by integrin-independent pathways. These studies provide well-controlled measures of how RGD ligands stimulate endocytosis. This may be of considerable interest for intracellular delivery of ligand-associated drugs in anti-angiogenic applications.},
	keywords = {alpha(v)beta(3) integrins, ALPHA-V-BETA-3, ANGIOGENESIS, ANTAGONISTS, ANTITUMOR EFFICACY, CELLS, Endocytosis, EXPRESSION, IN-VIVO, PEPTIDES, RGD, TARGETED DRUG-DELIVERY, TUMOR VASCULATURE},
	isbn = {1573-3149},
	url = {<Go to ISI>://000265022900007},
	author = {Cressman, S. and Sun, Y. and Maxwell, E. J. and Fang, N. and Chen, D. D. Y. and Cullis, P. R.}
}
