University of Wolverhampton
Browse
Collection All
bullet
bullet
bullet
bullet
Listed communities
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet
bullet

Wolverhampton Intellectual Repository and E-Theses > Research Institutes > Research Institute in Healthcare Science > Molecular Pharmacology Research Group > Chimeric peptides as tumour-selective delivery systems.

Please use this identifier to cite or link to this item: http://hdl.handle.net/2436/30277
    Del.icio.us     LinkedIn     Citeulike     Connotea     Facebook     Stumble it!



Title: Chimeric peptides as tumour-selective delivery systems.
Other Titles: In: Abstracts from the World Federation of Neuro-Oncology 2nd Quadrennial Meeting and the 6th Meeting of the European Association for Neuro-Oncology, Edinburgh, UK, 5-8 May 2005, No.373.
Authors: Jones, Sarah
Howl, John D.
Citation: Neuro-oncology, 7(3): 373
Publisher: Society for Neuro-oncology and Duke University Press
Journal: Neuro-oncology
Issue Date: 2005
URI: http://hdl.handle.net/2436/30277
DOI: 10.1215/ S1152851705200388
Additional Links: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1871910
Abstract: The cell-type-specific targeting of cytotoxic agents and other functional moieties can be achieved by using peptidyl address motifs that selectively bind protein targets expressed at high density at the cell membrane. Indeed, numerous studies have confirmed the utility of ligands for G protein–coupled receptors as components of heterofunctional peptide chimeras that are selective biological probes. Our current efforts are directed toward the further development of chimeric peptidyl constructs that employ sequences derived from GPCR ligands or cell penetrant motifs to affect the selective delivery of cytotoxins and signal transduction modulators to tumor cells. We have designed and synthesized a range of hybrid constructs consisting of cytotoxins (peptide and non-peptide) covalently linked to an address peptide derived from the C-terminal of gastrin (G7; H-AYGWMDF-NH2). The G7 homing motif targets a novel binding site expressed by U373MG astrocytic tumor cells that is distinct from classical CCK1/CCK2 receptors. Moreover, biological responses following activation of this novel membrane-bound protein may offer additional therapeutic advantages. For example, G7 receptor activation is reported to inhibit the motility of malignant astrocytoma in vivo while avoiding the growth-promoting effects of gastrin (Pannequin et al., J. Pharmacol. Exp. Ther. 302, 274, 2002). We evaluated the cytotoxicity of our chimeric peptides by comparing changes in cellular viability using MTT conversion assays. Our data indicate that chimeric peptides dose-dependently and rapidly (<8 h) reduced the viability of U373MG cells. Moreover, as a chimeric amino-terminal extension, the G7 address motif enhanced the cytotoxicity of both mastoparan (H-INLKALAALAKKIL-NH2) and D(KLAKLAK)2 peptides reported to stimulate necrosis and/or apoptosis of eukarytoic cells. In conclusion, hybrid G7 chimeras enhance the efficacy of cytotoxic agents and may be valuable probes to investigate and manipulate additional aspects of astrocytoma cell biology. This work was supported by The Wellcome Trust.
Type: Article
Language: en
Description: Abstracts from Neuro-Oncology are provided here courtesy of Society for Neuro-Oncology and Duke University Press.
Keywords: Cytotoxicity
Chimerism
Cell Penetrating Peptides (CPP)
CPP
Signal Transduction
Molecular Biology
Oncology
Astrocytoma
Brain Tumours
Ligands
Peptides
ISSN: 1522-8517
Appears in Collections: Molecular Pharmacology Research Group

Files in This Item:

There are no files associated with this item.



All Items in WIRE are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Fairtrade - Guarantees a better deal for Third World Producers

University of Wolverhampton, Wulfruna Street, Wolverhampton, WV1 1LY

Course enquiries: 0800 953 3222, General enquiries: 01902 321000,
Email: enquiries@wlv.ac.uk | Freedom of Information | Disclaimer and copyright | Website feedback | The University as a charity

OR Logo Powered by Open Repository | Cookies