title: 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.
abstract: 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.
authors.affiliation: Organic Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, Maharashtra, India.
authors.forename: Kiran M
authors.initials: KM
authors.lastname: Patil
authors.affiliation: Structural Biology Unit, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110025, India.
authors.forename: Rangeetha J
authors.initials: RJ
authors.lastname: Naik
authors.affiliation: Structural Biology Unit, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110025, India.
authors.forename: Manika
authors.initials: M
authors.lastname: Vij
authors.affiliation: Organic Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, Maharashtra, India.
authors.forename: Amit K
authors.initials: AK
authors.lastname: Yadav
authors.affiliation: Organic Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, Maharashtra, India.
authors.forename: Vaijayanti A
authors.initials: VA
authors.lastname: Kumar
authors.affiliation: Structural Biology Unit, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi 110025, India. Electronic address: mganguli@igib.in.
authors.forename: Munia
authors.initials: M
authors.lastname: Ganguli
authors.affiliation: Organic Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, Maharashtra, India. Electronic address: m.dcosta@ncl.res.in.
authors.forename: Moneesha
authors.initials: M
authors.lastname: Fernandes
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D003412:Cricetulus; D004247:DNA / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans
chemical_list: D000596:Amino Acids; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D004247:DNA
keywords: (R–X–R)-motif; Cell-penetrating peptide; Constrained chiral amino acid; Peptidomimetics; α–ω–α-Peptide