مورد إلكتروني
Novel nucleotide analogues for forming stable DNA triple helices
| العنوان: | Novel nucleotide analogues for forming stable DNA triple helices |
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| المؤلفون: | Gerrard, Simon Richard |
| بيانات النشر: | University of Southampton 2009-06 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | DNA triple helices are an important tool in a variety of medicinal and biotechnological applications, such as gene therapy and chemotherapeutics. DNA triple helices are formed by binding of a triplex-forming oligonucleotide (TFO) to a DNA duplex, via specific recognition of the individual base pairs in the target sequence. Mixed-sequence recognition of duplex DNA by TFOs is therefore an essential requirement for successful targeting. However, achieving strong, yet specific binding to the pyrimidine.purine (Py.Pu) base pairs CG and TA, by TFOs is a greater challenge than to the purine.pyrimidine (Pu.Py) base pairs (GC, AT), as fewer hydrogen bonds are presented for binding in the major groove of the double helix. Selective recognition of CG, could be achieved by utilising additional interactions across the CG base pair, via amino-modified nucleosides, to form more stable, selective triplets than those which can be formed by the natural base T. Four modified phosphoramidite monomers, meta-aminophenyl-modified analogues of the bicyclic nucleosides, (2,3H)-furano[2,3-d]pyrimidin-2(7H)-one and N-methyl-(2,3H)-pyrrolo- [2,3-d]pyrimidin-2(7H)-one, were synthesised to address this potential hydrogenbonding motif. Biophysical studies demonstrate selective recognition of the CG base pair. Results indicate selectivity for CG and binding affinity are much improved on previous modifications. Their fluorescence properties and general oligonucleotide deprotection conditions were also studied. In addition, the synthesis of a bis-amine modified 6-oxocytidine phosphoramidite monomer for GC recognition was re-investigated. This research shows significant advances in the field of triplexes for therapeutic use. |
| مصطلحات الفهرس: | Thesis, NonPeerReviewed |
| URL: | |
| الإتاحة: | Open access content. Open access content |
| ملاحظة: | text English |
| أرقام أخرى: | S2H oai:eprints.soton.ac.uk:69835 Gerrard, Simon Richard (2009) Novel nucleotide analogues for forming stable DNA triple helices. University of Southampton, School of Chemistry, Doctoral Thesis, 263pp. 1303706482 |
| المصدر المساهم: | UNIV OF SOUTHAMPTON, HARTLEY LIBR From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1303706482 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |