Cellular uptake of 2-aminopyridine-modified peptide nucleic acids conjugated with cell-penetrating peptides.
cellular uptake
confocal fluorescence microscopy
peptide nucleic acid
Journal
Biopolymers
ISSN: 1097-0282
Titre abrégé: Biopolymers
Pays: United States
ID NLM: 0372525
Informations de publication
Date de publication:
Apr 2022
Apr 2022
Historique:
revised:
30
11
2021
received:
19
05
2021
accepted:
06
12
2021
pubmed:
17
12
2021
medline:
29
4
2022
entrez:
16
12
2021
Statut:
ppublish
Résumé
Cell-penetrating peptides (CPPs) have been extensively used to deliver peptide nucleic acid (PNA) in cells. We have previously found that replacement of cytosine in triplex-forming PNAs with 2-aminopyridine (M) not only enhanced RNA binding, but also improved cellular uptake of PNAs. In this study, we used confocal fluorescence microscopy to evaluate the ability of CPPs to further improve cellular uptake of M-modified PNAs. We found that PNAs conjugated with Tat and octa-arginine peptides were effectively taken up in MCF7 cells when supplied in cell media at 1 μM. Remarkably, M-modified PNA without any CPP conjugation also showed strong uptake when the concentration was increased to 5 μM. Majority of PNA conjugates remained localized in distinct cytoplasmic vesicles, as judged by dot-like fluorescence patterns. However, M-modified PNAs conjugated with Tat, octa-arginine, and even a simple tri-lysine peptide also showed dispersed fluorescence in cytoplasm and were taken up in nuclei where they localized in larger vesicles, most likely nucleoli. Endosomolytic peptides or chemicals (chloroquine and CaCl
Identifiants
pubmed: 34914092
doi: 10.1002/bip.23484
pmc: PMC9050817
mid: NIHMS1763128
doi:
Substances chimiques
Aminopyridines
0
Cell-Penetrating Peptides
0
Peptide Nucleic Acids
0
RNA
63231-63-0
Arginine
94ZLA3W45F
alpha-aminopyridine
WSX981HEWU
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23484Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM130207
Pays : United States
Organisme : NIH HHS
ID : GM130207
Pays : United States
Informations de copyright
© 2021 Wiley Periodicals LLC.
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