Second generation, arginine-rich (R-X'-R)(4)-type cell-penetrating α-ω-α-peptides with constrained, chiral ω-amino acids (X') for enhanced cargo delivery into cells

The syntheses of novel N-aminoalkyl proline-derived spacers (X') in polycationic (R-X'-R)-motif cell-penetrating α-ω-α-peptides are described as improved molecular transporters and their structural features studied by CD. FACS analysis shows enhanced cellular uptake and confocal microscopy...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2014-09, Vol.24 (17), p.4198-4202
Main Authors: Patil, Kiran M, Naik, Rangeetha J, Vij, Manika, Yadav, Amit K, Kumar, Vaijayanti A, Ganguli, Munia, Fernandes, Moneesha
Format: Article
Language:English
Subjects:
Amino Acids - chemistry
Animals
Cell Line, Tumor
Cell Membrane Permeability - drug effects
Cell Survival - drug effects
Cell-Penetrating Peptides - chemistry
Cell-Penetrating Peptides - metabolism
Cell-Penetrating Peptides - pharmacology
CHO Cells
Cricetulus
DNA - metabolism
Drug Carriers - chemistry
Drug Carriers - metabolism
Drug Carriers - pharmacology
HeLa Cells
Humans
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Summary:The syntheses of novel N-aminoalkyl proline-derived spacers (X') in polycationic (R-X'-R)-motif cell-penetrating α-ω-α-peptides are described as improved molecular transporters and their structural features studied by CD. FACS analysis shows enhanced cellular uptake and confocal microscopy indicates predominantly cytoplasmic localization. The oligomers are efficient at transporting pDNA into cells. The chirality together with the hydrophobicity and flexibility derived from the spacer chain are found to have marked influence on the cell-penetrating and cargo delivery properties of the cell-penetrating peptides (CPPs). The peptides containing N-(3-aminopropyl)-D-proline spacers are found to be the best at cell penetration and cargo delivery in the present study.
ISSN:1464-3405
DOI:10.1016/j.bmcl.2014.07.040