Document Detail

Structural effects and lipid membrane interactions of the pH responsive GALA peptide with fatty acid acylation.
MedLine Citation:
PMID:  22591394     Owner:  NLM     Status:  Publisher    
GALA is a pH-responsive, membrane-perturbing peptide designed to fold from a random coil at physiological pH to an amphipathic α-helix under mildly acidic conditions. Due to its pH-activated function, GALA has been sought-after as a component of intracellular drug delivery systems that could actively propel endosomal escape. In this study, we conjugated GALA with lauryl and palmitoyl fatty acid tails, as model hydrophobic moieties and examined the physicochemical characteristics and activities of the resulting peptide amphiphiles (PAs). The fatty acid variants of GALA exhibited distinctly different membrane perturbing mechanisms at pH 7.5 and 5.5. At physiological pH, the PAs ruptured liposomes through a surfactant-like mechanism. At pH 5.5, lauryl-GALA was shown to form transmembrane pores with a higher potency as compared to its unmodified peptide counterpart; however, after prolonged exposure it also caused liposome lysis. The lytic activity of fatty acid-conjugated GALA did not impair cell viability. Lauryl-GALA was tolerated well by SJSA-1 osteocarcinoma cells and enhanced cell internalization of the PA was observed. Our findings are discussed with the overarching goal of developing efficient therapeutic delivery systems.
Brian F Lin; Dimitris Missirlis; Daniel V Krogstad; Matthew Tirrell
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-16
Journal Detail:
Title:  Biochemistry     Volume:  -     ISSN:  1520-4995     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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