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水溶性、中位取代的阳离子卟啉——一类用于寡核苷酸细胞递送的化合物。

Water-soluble, meso-substituted cationic porphyrins--a family of compounds for cellular delivery of oligonucleotides.

作者信息

Flynn S M, George S T, White L, Devonish W, Takle G B

机构信息

Innovir Laboratories, Wilmington, DE, USA.

出版信息

Biotechniques. 1999 Apr;26(4):736-42, 744, 746. doi: 10.2144/99264rr03.


DOI:10.2144/99264rr03
PMID:10343913
Abstract

The delivery of oligonucleotides to appropriate intracellular compartments is crucial to their development as tools in gene function studies and as therapeutics. Here, we report the characterization of meso-substituted cationic porphyrins as a large class of water-soluble reagents for oligonucleotide delivery. These porphyrins form non-covalent complexes with single-stranded oligonucleotides and deliver these molecules into the nuclei of cell lines in culture. The porphyrins protect oligonucleotides from nuclease degradation, and delivery is unaffected by the presence of serum. Delivery capacity is dependent on the charge ratio and concentration of the oligonucleotide and porphyrin used to form the complex, on the chemical substituents of the oligonucleotide and on the identity of the cationic porphyrin. This class of molecules provides a versatile set of water-soluble delivery reagents that could contribute to the development of oligonucleotide drugs.

摘要

将寡核苷酸递送至合适的细胞内区室对于其作为基因功能研究工具和治疗剂的开发至关重要。在此,我们报道了中位取代的阳离子卟啉作为一大类用于寡核苷酸递送的水溶性试剂的特性。这些卟啉与单链寡核苷酸形成非共价复合物,并将这些分子递送至培养的细胞系细胞核中。卟啉可保护寡核苷酸免受核酸酶降解,且血清的存在不影响递送。递送能力取决于用于形成复合物的寡核苷酸和卟啉的电荷比及浓度、寡核苷酸的化学取代基以及阳离子卟啉的特性。这类分子提供了一组通用的水溶性递送试剂,可有助于寡核苷酸药物的开发。

相似文献

[1]
Water-soluble, meso-substituted cationic porphyrins--a family of compounds for cellular delivery of oligonucleotides.

Biotechniques. 1999-4

[2]
Time-resolved microspectrofluorometry and fluorescence imaging techniques: study of porphyrin-mediated cellular uptake of oligonucleotides.

Ann N Y Acad Sci. 2008

[3]
Influence of the nature of the porphyrin ligand on the nuclease activity of metalloporphyrin-oligonucleotide conjugates designed with cationic, hydrophobic or anionic metalloporphyrins.

Nucleic Acids Res. 1997-3-1

[4]
Solid-phase introduction and intracellular photoinduced reaction of a water-soluble meso-tetracarboxyporphine conjugated to an antisense oligodeoxyribonucleotide.

Biochimie. 1993

[5]
Novel heterotopic colloids of anionic porphyrins entangled in cationic amphiphilic cyclodextrins: spectroscopic investigation and intracellular delivery.

Chemistry. 2003-12-5

[6]
5'-Porphyrin-oligonucleotide conjugates: neutral porphyrin-DNA interactions.

Org Lett. 2005-12-8

[7]
[Porphyrin derivatives of oligonucleotides. I. Synthesis of oligonucleotide derivatives bearing 2,4-di(alpha-(2-hydroxyethoxy)ethyl)- deuteroporphyrin IX or a metal complex of it and study of the oxidative modification of DNA by these derivatives].

Bioorg Khim. 1993-4

[8]
Cationic lipids, phosphatidylethanolamine and the intracellular delivery of polymeric, nucleic acid-based drugs (review).

Mol Membr Biol. 1998

[9]
Length and sequence effect on the B-Z transition of [d(A-T)] oligonucleotide induced by a cationic porphyrin.

Biophys Chem. 2016-12

[10]
Photodynamic studies and photoinactivation of Escherichia coli using meso-substituted cationic porphyrin derivatives with asymmetric charge distribution.

Photochem Photobiol. 2004

引用本文的文献

[1]
Binding of a Tricationic meso-Substituted Porphyrin to poly(A)⋅poly(U): an Experimental Study.

J Fluoresc. 2024-10-28

[2]
A Cationic Tetraphenylethene as a Light-Up Supramolecular Probe for DNA G-Quadruplexes.

Front Chem. 2019-7-11

[3]
Erratum to: Axial imidazole binding strengths in porphyrinoid cobalt(III) complexes as studied by tandem mass spectrometry.

J Am Soc Mass Spectrom. 2012-6-12

[4]
Axial imidazole binding strengths in porphyrinoid cobalt(III) complexes as studied by tandem mass spectrometry.

J Am Soc Mass Spectrom. 2012-4-12

[5]
The porphyrin TmPyP4 unfolds the extremely stable G-quadruplex in MT3-MMP mRNA and alleviates its repressive effect to enhance translation in eukaryotic cells.

Nucleic Acids Res. 2012-1-20

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