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1.
Bioorg Med Chem ; 25(7): 2244-2250, 2017 04 01.
Article in English | MEDLINE | ID: mdl-28279557

ABSTRACT

In this paper, we report structure-based rational design and physico-chemical and biological studies of novel pyrene excimer forming dual probes for visualization of intracellular RNAs. Herein, the probes based on 2'-O-methyl RNA with linkers of different structure and length between pyrene moiety and ribose are studied with respect to their hybridization and spectral properties. We found optimal linkers that provide more intense excimer emission (at ∼480nm) of RNA-bound probes; particularly, the length of the linker arm of the 3'-component of dual probes plays a key role in formation of pyrene excimer. Calculated molecular dynamics trajectories and probability distributions of pyrene-pyrene dimer formation upon hybridization of the dual probes with RNA target are in agreement with the obtained fluorescence spectroscopy data for the corresponding duplexes. Our study demonstrates the excellent binding properties of new dual probes to structured RNA and their feasibility for the visualization of intracellular RNA targets.


Subject(s)
Drug Design , Oligonucleotide Probes/chemistry , RNA/chemistry , Spectrometry, Fluorescence , Structure-Activity Relationship
2.
Bioorg Khim ; 37(2): 273-7, 2011.
Article in Russian | MEDLINE | ID: mdl-21721260

ABSTRACT

A series of novel fluorescent conjugates of oligo(2'-O-methylribonucleotides) containing the insertions of 2'bispyrenylmethylphosphorodiamidate derivatives of ribonucleosides (Urd, Cyd) were synthesized and their fluorescent properties were investigated. The possibility of detection of RNA transcript of 5'-terminal fragment of mRNA of multidrug resistance gene mdr1 (1-678) in solution using synthesized multipyrene probes was demonstrated.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Drug Resistance, Multiple/genetics , Fluorescent Dyes/chemical synthesis , Oligonucleotide Probes/chemical synthesis , RNA, Messenger/analysis , 5' Flanking Region/genetics , Animals , Cytidine/analogs & derivatives , Cytidine/chemical synthesis , Humans , In Vitro Techniques , Mutagenesis, Insertional , Pathology, Molecular , Uridine/analogs & derivatives , Uridine/chemical synthesis
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