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 > Charge delocalisation and the design of novel mastoparan analogues: enhanced cytotoxicity and secretory efficacy of [Lys5, Lys8, Aib10]MP.

Please use this identifier to cite or link to this item: http://hdl.handle.net/2436/15857
    Del.icio.us     LinkedIn     Citeulike     Connotea     Facebook     Stumble it!



Title: Charge delocalisation and the design of novel mastoparan analogues: enhanced cytotoxicity and secretory efficacy of [Lys5, Lys8, Aib10]MP.
Authors: Jones, Sarah
Howl, John D.
Citation: Regulatory Peptides, 121(1-3): 121-128
Publisher: Elsevier BV
Issue Date: 2004
URI: http://hdl.handle.net/2436/15857
DOI: 10.1016/j.regpep.2004.04.015
PubMed ID: 15256282
Additional Links: http://dx.doi.org/10.1016/j.regpep.2004.04.015
Abstract: The formation of an amphipathic helix is a major determinant of the biological activity of the tetradecapeptide mastoparan (MP). To address the functional significance of lysyl residues at positions 4, 11 and 12 of MP, we synthesised five novel analogues using sequence permutation and arginine-substitution to delocalise cationic charge. Comparative bioassays determined cytotoxicity, beta-hexoseaminidase secretory efficacy and peptide-activated extracellular receptor-stimulated kinase (ERK)1/2 phosphorylation. The monosubstitution of individual lysine residues with arginine produced differential changes to the indices of cytotoxicity and secretion indicating that these conservative substitutions are compatible with membrane translocation and the selective binding and activation of intracellular proteins. More profound changes to the predicted hydrophilic face of MP, resulting from the relocation or substitution of additional lysyl residues, enhanced both the cytotoxicity and secretory efficacy of novel peptides. Significantly, the more amphipathic peptide [Lys5, Lys8, Aib10]MP was identified to be both the most cytotoxic and the most potent secretagogue of all the peptides compared here. Charge delocalisation within the hydrophilic face of MP analogues was also compatible with peptide-induced activation of ERK1/2 phosphorylation. Our data indicate that charge delocalisation is a suitable strategy to engineer more potent analogues of MP that differentially target intracellular proteins.
Type: Article
Language: en
Description: Metadata only
Keywords: Charge delocalisation
Novel mastoparan analogues
Cytotoxicity
Secretory efficacy
Lys5, Lys8, Aib10]MP
Design
ISSN: 0167-0115
Appears in Collections: Molecular Pharmacology Research Group

Files in This Item:

There are no files associated with this item.



Related articles on PubMed
bullet
bullet
bullet
Novel mastoparan analogs induce differential secretion from mast cells.
Farquhar M, Soomets U, Bates RL, Martin A, Langel U, Howl J
2002 Jan
bullet
bullet
See all 80 articles

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