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      Molecular Beacons of Xeno-Nucleic Acid for Detecting Nucleic Acid

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          Abstract

          Molecular beacons (MBs) of DNA and RNA have aroused increasing interest because they allow a continuous readout, excellent spatial and temporal resolution to observe in real time. This kind of dual-labeled oligonucleotide probes can differentiate between bound and unbound DNA/RNA in homogenous hybridization with a high signal-to-background ratio in living cells. This review briefly summarizes the different unnatural sugar backbones of oligonucleotides combined with fluorophores that have been employed to sense DNA/RNA. With different probes, we epitomize the fundamental understanding of driving forces and these recognition processes. Moreover, we will introduce a few novel and attractive emerging applications and discuss their advantages and disadvantages. We also highlight several perspective probes in the application of cancer therapeutics.

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          Most cited references109

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          Molecular beacons: probes that fluoresce upon hybridization.

          We have developed novel nucleic acid probes that recognize and report the presence of specific nucleic acids in homogeneous solutions. These probes undergo a spontaneous fluorogenic conformational change when they hybridize to their targets. Only perfectly complementary targets elicit this response, as hybridization does not occur when the target contains a mismatched nucleotide or a deletion. The probes are particularly suited for monitoring the synthesis of specific nucleic acids in real time. When used in nucleic acid amplification assays, gene detection is homogeneous and sensitive, and can be carried out in a sealed tube. When introduced into living cells, these probes should enable the origin, movement, and fate of specific mRNAs to be traced.
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            PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules.

            DNA analogues are currently being intensely investigated owing to their potential as gene-targeted drugs. Furthermore, their properties and interaction with DNA and RNA could provide a better understanding of the structural features of natural DNA that determine its unique chemical, biological and genetic properties. We recently designed a DNA analogue, PNA, in which the backbone is structurally homomorphous with the deoxyribose backbone and consists of N-(2-aminoethyl)glycine units to which the nucleobases are attached. We showed that PNA oligomers containing solely thymine and cytosine can hybridize to complementary oligonucleotides, presumably by forming Watson-Crick-Hoogsteen (PNA)2-DNA triplexes, which are much more stable than the corresponding DNA-DNA duplexes, and bind to double-stranded DNA by strand displacement. We report here that PNA containing all four natural nucleobases hybridizes to complementary oligonucleotides obeying the Watson-Crick base-pairing rules, and thus is a true DNA mimic in terms of base-pair recognition.
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              Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide.

              A polyamide nucleic acid (PNA) was designed by detaching the deoxyribose phosphate backbone of DNA in a computer model and replacing it with an achiral polyamide backbone. On the basis of this model, oligomers consisting of thymine-linked aminoethylglycyl units were prepared. These oligomers recognize their complementary target in double-stranded DNA by strand displacement. The displacement is made possible by the extraordinarily high stability of the PNA-DNA hybrids. The results show that the backbone of DNA can be replaced by a polyamide, with the resulting oligomer retaining base-specific hybridization.
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                Author and article information

                Journal
                Theranostics
                Theranostics
                thno
                Theranostics
                Ivyspring International Publisher (Sydney )
                1838-7640
                2013
                5 May 2013
                : 3
                : 6
                : 395-408
                Affiliations
                1. Key Lab for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, China.
                2. College of Public Health, Nantong University, China.
                Author notes
                ✉ Corresponding author: Junchen Wu, Meilong 130, Shanghai 200237, China. Telephone: (+86) 21-6425-3674, fax: (+86) 21-6425-2258, E-mail: jcwu@ 123456ecust.edu.cn .

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                thnov03p0395
                10.7150/thno.5935
                3677410
                23781286
                6afb273c-5c63-4855-b0dd-38ae9afb9463
                © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
                History
                : 23 January 2013
                : 10 April 2013
                Categories
                Review

                Molecular medicine
                xeno-nucleic acid,nucleic acid,molecular beacon,diagnostics.
                Molecular medicine
                xeno-nucleic acid, nucleic acid, molecular beacon, diagnostics.

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