Document Detail

Quantifying molecular partition of cell-penetrating peptide-cargo supramolecular complexes into lipid membranes: optimizing peptide-based drug delivery systems.
MedLine Citation:
PMID:  23322613     Owner:  NLM     Status:  Publisher    
One of the major challenges in the drug development process is biodistribution across epithelia and intracellular drug targeting. Cellular membrane heterogeneity is one of the major drawbacks in developing efficient and sustainable drug delivery systems, which brings the need to study their interaction with lipids in order to unravel their mechanisms of action and improve their delivery capacities. Cell penetrating peptides (CPPs) are able to translocate almost any cell membrane carrying cargo molecules. However, different CPP use different entry mechanisms, which are often concentration-dependent and cargo-dependent. Being able to quantify the lipid affinity of CPP is of obvious importance and can be achieved by studying the partition extent of CPP into lipid bilayers. The partition constant (K(p) ) reflects the lipid-water partition extent. However, all currently available methodologies are only suitable to determine the partition of single molecules into lipid membranes or entities, being unsuitable to determine the partition of bimolecular or higher order supramolecular complexes. We derived and tested a mathematical model to determine the K(p) of supramolecular CPP-cargo complexes from fluorescence spectroscopy data, using DNA oligomers as a model cargo. As a proof-of-concept example, the partition extent of two new membrane active peptides derived from dengue virus capsid protein (DENV C protein) with potential CPP properties, in both scenarios (free peptide and complexed with a molecular cargo), were tested. We were able to identify the lipid affinity of these CPP:DNA complexes, thus gaining valuable insights into better CPP formulations. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.
João Miguel Freire; Ana Salomé Veiga; Beatriz G de la Torre; David Andreu; Miguel A R B Castanho
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-16
Journal Detail:
Title:  Journal of peptide science : an official publication of the European Peptide Society     Volume:  -     ISSN:  1099-1387     ISO Abbreviation:  J. Pept. Sci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9506309     Medline TA:  J Pept Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.
Instituto de Medicina Molecular, University of Lisbon, Physical Biochemistry Unit, Lisbon, Portugal.
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