Artificial DNA: PNA & XNA最新文献

Effect of 2′-O-methyl/thiophosphonoacetate-modified antisense oligonucleotides on huntingtin expression in patient-derived cells 2 ' - o -甲基/硫代膦酸酯修饰的反义寡核苷酸对患者源性细胞中亨廷顿蛋白表达的影响

Artificial DNA: PNA & XNA Pub Date : 2014-12-15 DOI: 10.1080/1949095X.2016.1146391

Masayuki Matsui, Richard Threlfall, M. Caruthers, D. Corey

引用次数: 3

Effect of chirality in gamma-PNA: PNA interaction, another piece in the picture. 伽马-PNA：PNA 相互作用中手性的影响，图片中的另一块。

Artificial DNA: PNA & XNA Pub Date : 2014-12-15 DOI: 10.1080/1949095X.2015.1131801

Alex Manicardi, Roberto Corradini

引用次数: 0

Insights on chiral, backbone modified peptide nucleic acids: Properties and biological activity. 对手性、主链修饰肽核酸的见解:性质和生物活性。

Artificial DNA: PNA & XNA Pub Date : 2014-12-15 Epub Date: 2016-01-11 DOI: 10.1080/1949095X.2015.1107176

Maria Moccia, Mauro F A Adamo, Michele Saviano

引用次数: 22

Purification and assembly of thermostable Cy5 labeled γ-PNAs into a 3D DNA nanocage. 纯化可恒温 Cy5 标记的 γ-PNA 并将其组装到三维 DNA 纳米笼中。

Artificial DNA: PNA & XNA Pub Date : 2014-12-15

Justin D Flory, Trey Johnson, Chad D Simmons, Su Lin, Giovanna Ghirlanda, Petra Fromme

{"title":"Purification and assembly of thermostable Cy5 labeled γ-PNAs into a 3D DNA nanocage.","authors":"Justin D Flory, Trey Johnson, Chad D Simmons, Su Lin, Giovanna Ghirlanda, Petra Fromme","doi":"","DOIUrl":"","url":null,"abstract":"PNA is hybrid molecule ideally suited for bridging the functional landscape of polypeptides with the structural diversity that can be engineered with DNA nanostructures. However, PNA can be more challenging to work with in aqueous solvents due to its hydrophobic nature. A solution phase method using strain promoted, copper free click chemistry was developed to conjugate the fluorescent dye Cy5 to 2 bifunctional PNA strands as a first step toward building cyclic PNA-polypeptides that can be arranged within 3D DNA nanoscaffolds. A 3D DNA nanocage was designed with binding sites for the 2 fluorescently labeled PNA strands in close proximity to mimic protein active sites. Denaturing polyacrylamide gel electrophoresis (PAGE) is introduced as an efficient method for purifying charged, dye-labeled NA conjugates from large excesses of unreacted dye and unreacted, neutral PNA. Elution from the gel in water was monitored by fluorescence and found to be more efficient for the more soluble PNA strand. Native PAGE shows that both PNA strands hybridize to their intended binding sites within the DNA nanocage. Förster resonance energy transfer (FRET) with a Cy3 labeled DNA nanocage was used to determine the dissociation temperature of one PNA-Cy5 conjugate to be near 50C. Steady-state and time resolved fluorescence was used to investigate the dye orientation and interactions within the various complexes. Bifunctional, thermostable PNA molecules are intriguing candidates for controlling the assembly and orientation of peptides within small DNA nanocages for mimicking protein catalytic sites.","PeriodicalId":8444,"journal":{"name":"Artificial DNA: PNA & XNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5329897/pdf/kdpx-05-03-992181.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34680534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anomeric DNA quadruplexes. 异头DNA四联体。

Artificial DNA: PNA & XNA Pub Date : 2014-01-01 DOI: 10.4161/adna.28422

Natalia A Kolganova, Anna M Varizhuk, Roman A Novikov, Vladimir L Florentiev, Galina E Pozmogova, Olga F Borisova, Anna K Shchyolkina, Igor P Smirnov, Dmitry N Kaluzhny, Edward N Timofeev

{"title":"Anomeric DNA quadruplexes.","authors":"Natalia A Kolganova, Anna M Varizhuk, Roman A Novikov, Vladimir L Florentiev, Galina E Pozmogova, Olga F Borisova, Anna K Shchyolkina, Igor P Smirnov, Dmitry N Kaluzhny, Edward N Timofeev","doi":"10.4161/adna.28422","DOIUrl":"https://doi.org/10.4161/adna.28422","url":null,"abstract":"Thrombin-binding aptamer (TBA) is a 15-nt DNA oligomer that efficiently inhibits thrombin. It has been shown that TBA folds into an anti-parallel unimolecular G-quadruplex. Its three-dimensional chair-like structure consists of two G-tetrads connected by TT and TGT loops. TBA undergoes fast degradation by nucleases in vivo. To improve the nuclease resistance of TBA, a number of modified analogs have been proposed. Here, we describe anomeric modifications of TBA. Non-natural α anomers were used to replace selected nucleotides in the loops and core. Significant stabilization of the quadruplex was observed for the anomeric modification of TT loops at T4 and T13. Replacement of the core guanines either prevents quadruplex assembly or induces rearrangement in G-tetrads. It was found that the anticoagulant properties of chimeric aptamers could be retained only with intact TT loops. On the contrary, modification of the TGT loop was shown to substantially increase nuclease resistance of the chimeric aptamer without a notable disturbance of its anticoagulant activity. ","PeriodicalId":8444,"journal":{"name":"Artificial DNA: PNA & XNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/adna.28422","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32887530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Purification and assembly of thermostable Cy5 labeled γ-PNAs into a 3D DNA nanocage. 高温Cy5标记γ-PNAs的纯化和组装成三维DNA纳米笼。

Artificial DNA: PNA & XNA Pub Date : 2014-01-01 DOI: 10.4161/1949095X.2014.992181

Justin D Flory, Trey Johnson, Chad R Simmons, Su Lin, Giovanna Ghirlanda, Petra Fromme

{"title":"Purification and assembly of thermostable Cy5 labeled γ-PNAs into a 3D DNA nanocage.","authors":"Justin D Flory, Trey Johnson, Chad R Simmons, Su Lin, Giovanna Ghirlanda, Petra Fromme","doi":"10.4161/1949095X.2014.992181","DOIUrl":"https://doi.org/10.4161/1949095X.2014.992181","url":null,"abstract":"PNA is hybrid molecule ideally suited for bridging the functional landscape of polypeptides with the structural diversity that can be engineered with DNA nanostructures. However, PNA can be more challenging to work with in aqueous solvents due to its hydrophobic nature. A solution phase method using strain promoted, copper free click chemistry was developed to conjugate the fluorescent dye Cy5 to 2 bifunctional PNA strands as a first step toward building cyclic PNA-polypeptides that can be arranged within 3D DNA nanoscaffolds. A 3D DNA nanocage was designed with binding sites for the 2 fluorescently labeled PNA strands in close proximity to mimic protein active sites. Denaturing polyacrylamide gel electrophoresis (PAGE) is introduced as an efficient method for purifying charged, dye-labeled PNA conjugates from large excesses of unreacted dye and unreacted, neutral PNA. Elution from the gel in water was monitored by fluorescence and found to be more efficient for the more soluble PNA strand. Native PAGE shows that both PNA strands hybridize to their intended binding sites within the DNA nanocage. Förster resonance energy transfer (FRET) with a Cy3 labeled DNA nanocage was used to determine the dissociation temperature of one PNA-Cy5 conjugate to be near 50°C. Steady-state and time resolved fluorescence was used to investigate the dye orientation and interactions within the various complexes. Bifunctional, thermostable PNA molecules are intriguing candidates for controlling the assembly and orientation of peptides within small DNA nanocages for mimicking protein catalytic sites. ","PeriodicalId":8444,"journal":{"name":"Artificial DNA: PNA & XNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/1949095X.2014.992181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33120586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Universal strategies for the DNA-encoding of libraries of small molecules using the chemical ligation of oligonucleotide tags. 利用寡核苷酸标签的化学连接对小分子文库进行dna编码的通用策略。

Artificial DNA: PNA & XNA Pub Date : 2014-01-01 DOI: 10.4161/adna.27896

Alexander Litovchick, Matthew A Clark, Anthony D Keefe

{"title":"Universal strategies for the DNA-encoding of libraries of small molecules using the chemical ligation of oligonucleotide tags.","authors":"Alexander Litovchick, Matthew A Clark, Anthony D Keefe","doi":"10.4161/adna.27896","DOIUrl":"https://doi.org/10.4161/adna.27896","url":null,"abstract":"The affinity-mediated selection of large libraries of DNA-encoded small molecules is increasingly being used to initiate drug discovery programs. We present universal methods for the encoding of such libraries using the chemical ligation of oligonucleotides. These methods may be used to record the chemical history of individual library members during combinatorial synthesis processes. We demonstrate three different chemical ligation methods as examples of information recording processes (writing) for such libraries and two different cDNA-generation methods as examples of information retrieval processes (reading) from such libraries. The example writing methods include uncatalyzed and Cu(I)-catalyzed alkyne-azide cycloadditions and a novel photochemical thymidine-psoralen cycloaddition. The first reading method \"relay primer-dependent bypass\" utilizes a relay primer that hybridizes across a chemical ligation junction embedded in a fixed-sequence and is extended at its 3'-terminus prior to ligation to adjacent oligonucleotides. The second reading method \"repeat-dependent bypass\" utilizes chemical ligation junctions that are flanked by repeated sequences. The upstream repeat is copied prior to a rearrangement event during which the 3'-terminus of the cDNA hybridizes to the downstream repeat and polymerization continues. In principle these reading methods may be used with any ligation chemistry and offer universal strategies for the encoding (writing) and interpretation (reading) of DNA-encoded chemical libraries. ","PeriodicalId":8444,"journal":{"name":"Artificial DNA: PNA & XNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/adna.27896","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32888113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 16

The genetic code. Rewritten, revised, repurposed. 遗传密码。重写，修改，改变用途。

Artificial DNA: PNA & XNA Pub Date : 2014-01-01 DOI: 10.4161/adna.29408

Roy D Sleator

引用次数: 4

Improved bioactivity of G-rich triplex-forming oligonucleotides containing modified guanine bases. 含有修饰鸟嘌呤碱基的富g三聚体寡核苷酸生物活性的提高。

Artificial DNA: PNA & XNA Pub Date : 2014-01-01 DOI: 10.4161/adna.27792

Faye A Rogers, Janice A Lloyd, Meetu Kaushik Tiwari

{"title":"Improved bioactivity of G-rich triplex-forming oligonucleotides containing modified guanine bases.","authors":"Faye A Rogers, Janice A Lloyd, Meetu Kaushik Tiwari","doi":"10.4161/adna.27792","DOIUrl":"https://doi.org/10.4161/adna.27792","url":null,"abstract":"Triplex structures generated by sequence-specific triplex-forming oligonucleotides (TFOs) have proven to be promising tools for gene targeting strategies. In addition, triplex technology has been highly utilized to study the molecular mechanisms of DNA repair, recombination and mutagenesis. However, triplex formation utilizing guanine-rich oligonucleotides as third strands can be inhibited by potassium-induced self-association resulting in G-quadruplex formation. We report here that guanine-rich TFOs partially substituted with 8-aza-7-deaza-guanine (PPG) have improved target site binding in potassium compared with TFOs containing the natural guanine base. We designed PPG-substituted TFOs to bind to a polypurine sequence in the supFG1 reporter gene. The binding efficiency of PPG-substituted TFOs to the target sequence was analyzed using electrophoresis mobility gel shift assays. We have determined that in the presence of potassium, the non-substituted TFO, AG30 did not bind to its target sequence, however binding was observed with the PPG-substituted AG30 under conditions with up to 140 mM KCl. The PPG-TFOs were able to maintain their ability to induce genomic modifications as measured by an assay for gene-targeted mutagenesis. In addition, these compounds were capable of triplex-induced DNA double strand breaks, which resulted in activation of apoptosis. ","PeriodicalId":8444,"journal":{"name":"Artificial DNA: PNA & XNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/adna.27792","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32889691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Synthesis and spectral characterization of environmentally responsive fluorescent deoxycytidine analogs. 环境响应型荧光脱氧胞苷类似物的合成与光谱表征。

Artificial DNA: PNA & XNA Pub Date : 2014-01-01 DOI: 10.4161/adna.29174

Adam A H Elmehriki, Mojmír Suchý, Kirby J Chicas, Filip Wojciechowski, Robert H E Hudson

{"title":"Synthesis and spectral characterization of environmentally responsive fluorescent deoxycytidine analogs.","authors":"Adam A H Elmehriki, Mojmír Suchý, Kirby J Chicas, Filip Wojciechowski, Robert H E Hudson","doi":"10.4161/adna.29174","DOIUrl":"https://doi.org/10.4161/adna.29174","url":null,"abstract":"Herein, we describe the synthesis and spectroscopic properties of five novel pyrrolodeoxycytidine analogs, and the related 5-(1-pyrenylethynyl)-2'-deoxycytidine analog; as well as fluorescence characterization of 5-(p-methoxyphenylethynyl)-2'-deoxyuridine. Within this series of compounds, rigidification of the structure from 6-phenylpyrrolodeoxycytidine to 5,6-benzopyrroldeoxycytidine made remarkable improvement of the fluorescence quantum yield (Φ ~1, EtOH) and substantially increased the Stokes shift. Exchange of the phenyl group of 6-phenylpyrrolodeoxycytidine for other heterocycles (benzofuryl or indolyl) produced an increase in the extinction coefficient at the excitation wavelength while preserving high quantum yields. The steady-state fluorescence response to the environment was determined by sensitivity of Stokes shift to solvent polarity. The effect of solvent polarity on fluorescence emission intensity was concurrently examined and showed that 5,6-benzopyrrolodeoxycytidine is highly sensitive to the presence of water. On the other hand, the previously synthesized 5-(p-methoxyphenylethynyl)-2'-deoxyuridine was found to be sensitive to solvent viscosity indicating molecular rotor behavior. ","PeriodicalId":8444,"journal":{"name":"Artificial DNA: PNA & XNA","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4161/adna.29174","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32887531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7