Delivery of antisense peptide nucleic acids (PNAs) to the cytosol by disulphide conjugation to a lipophilic cation

FEBS Letters

Eccles, Michael R¹  Smith, Robin A.J³  Filipovska, Aleksandra²  Murphy, Michael P² 

[1] Department of Pathology, Medical School, University of Otago, P.O. Box 913, Dunedin, New Zealand;Medical Research Council Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 2XY, UK;Department of Chemistry, University of Otago, P.O. Box 956, Dunedin, New Zealand

关键词: Peptide nucleic acid;    Antisense;    Lipophilic cation;    Cell delivery;    Disulphide;    βm;    β2-microglobulin;    bio;    biotin;    bisTBTP;    bis-[(4-thiobutyl)triphenylphosphonium];    DMEM;    Dulbecco's modified Eagle's medium;    FCCP;    carbonylcyanide-p-trifluoromethoxyphenylhydrazone;    flu;    fluorescein;    PNA;    peptide nucleic acid;    PNAsh;    PNA incorporating a C-terminal cysteine;    PNAssTBTP;    PNAsh disulphide conjugated to TBTP;    TBTP;    4-thiobutyltriphenylphosphonium;    TPP;    triphenylphosphonium cation;   

DOI  :  10.1016/S0014-5793(03)01403-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Peptide nucleic acids (PNAs) are effective antisense reagents that bind specific mRNAs preventing their translation. However, PNAs cannot cross cell membranes, hampering delivery to cells. To overcome this problem we made PNAs membrane-permeant by conjugation to the lipophilic triphenylphosphonium (TPP) cation through a disulphide bond. The TPP cation led to efficient PNA uptake into the cytoplasm where the disulphide bond was reduced, releasing the antisense PNA to block expression of its target gene. This method of directing PNAs into cells is a significant improvement on current procedures and will facilitate in vitro and pharmacological applications of PNAs.

【 授权许可】

Unknown