Cellular import mediated by nuclear localization signal Peptide sequences.
The cellular delivery of therapeutic agents and their localization within cells is currently a great challenge in medicinal chemistry. A few cationic peptides have shown a strong propensity to cross the cytoplasmic membrane and enter cells. Nuclear localization signal (NLS) sequences are a class of highly cationic peptides that may be exploited for cellular import of linked cargo. A series of NLS sequence peptides were investigated for entry into different cancer cell lines by flow cytometry and confocal microscopy. All NLS peptides demonstrated rapid accumulation within cells when added to the cellular media. Covalent adducts of proteins and oligonucleotides with NLS peptides were also effectively imported within cells. An understanding of the structural and mechanistic properties of these sequences will provide great potential for the rational design of efficient and selective peptidic delivery systems.
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Angela D
AD
Ragin
Rashida A
RA
Morgan
Jean
J
Chmielewski
D002451:Cell Compartmentation; D016503:Drug Delivery Systems / Q000379:methods*; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D018613:Microscopy, Confocal; D019913:Nuclear Localization Signals / Q000737:chemistry / Q000493:pharmacokinetics*; D009841:Oligonucleotides / Q000737:chemistry / Q000493:pharmacokinetics; D014157:Transcription Factors / Q000737:chemistry; D014407:Tumor Cells, Cultured
D005456:Fluorescent Dyes; D019913:Nuclear Localization Signals; D009841:Oligonucleotides; D014157:Transcription Factors