Document Detail


Cationic amphiphilic polyproline helices: side-chain variations and cell-specific internalization.
MedLine Citation:
PMID:  19152633     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cell-penetrating peptides present an attractive and efficient tool for the delivery of a variety of cell impermeable cargoes across the cellular membrane. Cell-penetrating peptides usually consist of short basic peptide sequences that are internalized by a variety of cell lines. Most cell-penetrating peptides lack cell specificity, however, which greatly limits their use as efficient therapeutic agents. Herein, we present two cell-penetrating peptides displaying a type II polyproline helical backbone that are functionalized to contain six cationic moieties and two distinctive hydrophobic functionalities, namely isobutyl or benzyl groups. The uptake efficiency of these cationic amphiphilic polyproline helices was studied in seven different cell lines, six cancerous (MCF-7, HOS, HT1080, HeLa, KB-FD, KB3-1) and one non-cancerous (WI 38). The cationic amphiphilic polyproline helix P11LRR at 50 microM showed high specificity toward MCF-7 breast cancer cells. Co-culture experiments with P11LRR demonstrated almost exclusive internalization by MCF-7 cells and not WI38. The replacement of the isobutyl hydrophobic group with a benzyl moiety resulted in a shift in uptake efficiency and specificity across some cell lines. These results demonstrate that the type of hydrophobic residues utilized in the creation of cell-penetrating peptides can strongly influence the extent and specificity of cellular internalization.
Authors:
Iris Geisler; Jean Chmielewski
Related Documents :
7029713 - Vertebrate cell cycle modulates infection by protozoan parasites.
19688723 - Folate-conjugated micelles and their folate-receptor-mediated endocytosis.
2416473 - Growth inhibition of transformed cells correlates with their junctional communication w...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Chemical biology & drug design     Volume:  73     ISSN:  1747-0285     ISO Abbreviation:  -     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-20     Completed Date:  2009-02-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101262549     Medline TA:  Chem Biol Drug Des     Country:  England    
Other Details:
Languages:  eng     Pagination:  39-45     Citation Subset:  IM    
Affiliation:
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Cations / chemistry*
Cell Line
Cell Survival
Endocytosis / physiology*
Flow Cytometry
Humans
Molecular Structure
Peptides* / chemistry,  metabolism
Protein Structure, Secondary*
Surface-Active Agents / chemistry*
Chemical
Reg. No./Substance:
0/Cations; 0/Peptides; 0/Surface-Active Agents; 25191-13-3/polyproline

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Conformational dynamics of the flexible catalytic loop in Mycobacterium tuberculosis 1-deoxy-D-xylul...
Next Document:  The structural and functional role of the B-chain C-terminal arginine in the relaxin-3 peptide antag...