Thio-Ether Nucleic Acids: Clicking Together Synthetic Poly(Nucleic Acids)

硫醚核酸：点击在一起合成聚（核酸）

基本信息

批准号：
8440227
负责人：
Christopher N Bowman
金额：
$ 17.92万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-01 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8440227
关键词：
Acrylates Adenine Amino Acids Base Pair Mismatch Base Pairing Base Sequence Behavior Binding Biological Biological Assay Biological Process Characteristics Chemicals Chemistry Codon Nucleotides Complementary DNA Cytosine DNA DNA Binding DNA Sequence Detection Devices Diagnosis Disease Drug Delivery Systems Enzymes Ethers Forms Controls Gene Mutation Genetic Genetic Markers Genetic Materials Genetic Transcription Genomics Guanine In Vitro KRAS2 gene Lead Malignant Neoplasms Mediating Molecular Structure Molecular Weight Mutation Nanostructures Nature Nucleic Acid Hybridization Nucleic Acids Nucleic acid sequencing Oligonucleotides Oncogenes Peptide Nucleic Acids Peptide Synthesis Phase Production RNA Reaction Research Resistance Science Single Nucleotide Polymorphism Solid Solutions Specificity Structure Sulfhydryl Compounds Temperature Thymine Translations Treatment outcome Vertebral column Work aptamer base biological systems cancer diagnosis cost design disease diagnosis drug development in vivo knockout gene monomer nanoscale nanostructured novel nucleic acid structure public health relevance synthetic peptide

项目摘要

DESCRIPTION (provided by applicant): DNA represents one of the most capable and powerful biomolecular structures: functional as genetic material, hybridizing to complementary strands, being functional as aptamers, and active in transcription and translation as well as being capable of inducing organization and enabling the formation of designed nanostructures. DNA performs numerous natural biological functions as well as being used in drug development, biodetection, gene knockout, and genomics assays as well as many others. Despite these capabilities, DNA remains prohibitively expensive and/or difficult to implement for use in any but the most valuable applications, particularly in the materials realm. The overall hypothesis of the proposed research is that the synergistic combination of thiol-ene-based click chemistry with oligonucleotide synthesis will lead to the formation of an entirely new and highly capable class of oligonucleotide structures, i.e., thio-ether nucleic acids (TNAs), that are capable of interacting with sequence specificity with DNA in vivo, in vitro and in biofunctional applications such as biodetection and as aptamer mimics. The synergistic combination of thiol-ene click chemistry with synthetic oligonucleotide production will yield functional oligonucleotides that have enhanced DNA-binding capability, are easier to produce at scale, and have distinct chemical advantages over DNA and PNA structures. Broadly, the overall aim of this project is to develop and perform preliminary characterization of an entirely new class of oligonucleotide molecules that would have significant advantages over both biological oligonucleotides (DNA and RNA) as well as the synthetic PNAs for DNA hybridization, for biodetection, and for other biofunctional applications. The specific aims of this work are to (i) synthesize base-functionalized TNA monomers, (ii) form controlled sequence oligomers from these monomers and evaluate their capacity for strong, selective hybridization with DNA, and (iii) demonstrate the utility of these TNA sequences in SNP detection of the KRAS oncogene.

描述（由申请人提供）：DNA代表最有能力和功能最强大的生物分子结构之一：充当遗传物质，与互补链杂交，充当适体功能，并在转录和翻译中活跃，并能够诱导组织并促进设计的纳米结构的形成。 DNA执行许多自然生物学功能，并用于药物开发，生物调节，基因敲除和基因组学测定以及许多其他方法。尽管有这些功能，但除了最有价值的应用，尤其是在材料领域中，DNA仍然过于昂贵和/或难以实施以供任何最有价值的应用中使用。拟议的研究的总体假设是，基于硫醇 - 基于硫醇的点击化学与寡核苷酸合成的协同组合将导致形成全新且功能高度高度强大的一类寡核苷酸结构，即，即硫醚核酸（TNAS），与Biorcence Temence and Inuctiontions与DNA相互作用，并与DNA相互作用，VIV与VIV相互作用。生物调整和适体模仿。硫醇 - 烯单击化学与合成寡核苷酸产生的协同组合将产生具有增强DNA结合能力的功能性寡核苷酸，更易于在大规模上产生，并且比DNA和PNA结构具有明显的化学优势。从广义上讲，该项目的总体目的是开发和执行一类全新的寡核苷酸分子的初步表征，这些分子比生物寡核苷酸（DNA和RNA）具有显着优势，以及用于生物探测的DNA杂交的合成PNA，用于生物杂音，以及其他生物功能。这项工作的具体目的是（i）合成碱官能化的TNA单体，（ii）来自这些单体的受控序列低聚物，并评估它们与DNA强，选择性杂交的能力，（iii）在SNP中检测这些TNA序列的实用性。