The Chemical Biology of Aptamers: Synthesis and Applications

Mayer, Günter; Wulffen, Bernhard

doi:10.1002/9780470664001.ch18

Cited by 5 publications

(4 citation statements)

References 225 publications

(171 reference statements)

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“…If this structure were fully extended, hydrophobic pockets between the base-pair steps would be unfavourable, therefore the structure is twisted, releasing the water molecules and enhancing the pi-stacking interactions between neighboring base pairs, yielding the well known structure of double helix. This helix has two asymmetrical grooves, the major groove, which is wide and shallow, more able to interact with proteins, whereas the minor groove is narrow and deep, more able to interact with small molecules such as ligands or drugs [16].…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics simulations of structural and dynamical aspects of DNA hydration water

Netz¹

2022

J. Phys.: Condens. Matter

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Water is a remarkable liquid, both because of it is intriguing but also because of its importance. Water plays a key role on the structure and function of biological molecules, but on the other hand also the structure and dynamics of water are deeply influenced by its interactions with biological molecules, specially at low temperatures, where water’s anomalies are enhanced. Here we present extensive molecular dynamics simulations of water hydrating a oligonucleotide down to very low temperatures (supercooled water), comparing four water models and analyzing the water structure and dynamics in different domains: water in the minor groove, water in the major groove and bulk water. We found that the water in the grooves is slowed down by the interactions with the nucleic acid and a hints of a dynamic transition regarding translational and orientational dynamics were found, specially for the water models TIP4P/2005 and TIP4P-Ew, which also showed the closest agreement with available experimental data. The behavior of water in such extreme conditions is relevant for the study of cryopreservation of biological tissues.

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Section: Introductionmentioning

confidence: 99%

Molecular dynamics simulations of structural and dynamical aspects of DNA hydration water

Netz¹

2022

J. Phys.: Condens. Matter

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“…67-69 In this account, we are focusing on applications of the photocaged nucleobase approach to select examples of the light-regulation of biological processes in our lab.…”

Section: Introductionmentioning

confidence: 99%

“…Different aspects of the photoregulation of oligonucleotide function have been summarized in the literature, and the interested reader is directed to those reviews in order to obtain a comprehensive overview of the field. − In this Account, we focus on applications of the photocaged nucleobase approach to select examples of the light regulation of biological processes in our laboratory.…”

Section: Introductionmentioning

confidence: 99%

Optochemical Control of Deoxyoligonucleotide Function via a Nucleobase-Caging Approach

2013

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Conspectus Synthetic oligonucleotides have been extensively applied to control a wide range of biological processes such as gene expression, gene repair, DNA replication, and protein activity. Based on well-established sequence design rules that typically rely on Watson-Crick base pairing interactions researchers can readily program the function of these oligonucleotides. Therefore oligonucleotides provide a flexible platform for targeting a wide range of biological molecules, including DNA, RNA, and proteins. In addition, oligonucleotides are commonly used research tools in cell biology and developmental biology. However, a lack of conditional control methods has hampered the precise spatial and temporal regulation of oligonucleotide activity, which limits the application of these reagents to investigate complex biological questions. Nature controls biological function with a high level of spatial and temporal resolution and in order to elucidate the molecular mechanism of biological processes, researchers need tools that allow for the perturbation of these processes with Nature's precision. Light represents an excellent external regulatory element as irradiation can be easily controlled spatially and temporally. Thus, researchers have developed several different methods to conditionally control oligonucleotide activity with light. One of the most versatile strategies is optochemical regulation through the installation and removal of photo-labile caging groups on oligonucleotides. To produce switches that can control nucleic acid function with light, chemists introduce caging groups into the oligomer backbone or on specific nucleobases to block oligonucleotide function until the caging groups are removed by light exposure. In this Account, we focus on the application of caged nucleobases to the photo-regulation of DNA function. Using this approach we have both optochemically activated and deactivated gene expression at the transcriptional and translational level with spatial and temporal control. Specifically, we have used caged triplex-forming oligomers and DNA decoys to regulate transcription, and we have regulated translation with light-activated antisense agents. Moreover, we also discuss strategies that can trigger DNA enzymatic activity, DNA amplification, and DNA mutagenesis by light illumination. More recently, we have developed light-activated DNA logic operations, an advance that may lay the foundation for the optochemical control of complex DNA calculations.

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“…This extensive biology necessitates the development of tools for studying their recognition features as well as their utilization and alteration by endogenous and exogenous agents. [1] Emissive nucleoside analogues, when judiciously fabricated and incorporated, could serve as effective photophysical and mechanistic probes. [2] Extensive efforts have indeed been dedicated to the development and refinement of such means.…”

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confidence: 99%

Emissive Synthetic Cofactors: Enzymatic Interconversions of ^tzA Analogues of ATP, NAD⁺, NADH, NADP⁺, and NADPH

et al. 2017

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A series of enzymatic transformations, which generate visibly emissive isofunctional cofactors based on an isothiazolo[4,3-d]pyrimidine analogue of adenosine ( A), was developed. Nicotinamide adenylyl transferase condenses nicotinamide mononucleotide and ATP to yield N AD , which can be enzymatically phosphorylated by NAD kinase and ATP or ATP to the corresponding N ADP . The latter can be engaged in NADP-specific coupled enzymatic transformations involving conversion to N ADPH by glucose-6-phosphate dehydrogenase and reoxidation to N ADP by glutathione reductase. The N ADP /N ADPH cycle can be monitored in real time by fluorescence spectroscopy.

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The Chemical Biology of Aptamers: Synthesis and Applications

Cited by 5 publications

References 225 publications

Molecular dynamics simulations of structural and dynamical aspects of DNA hydration water

Molecular dynamics simulations of structural and dynamical aspects of DNA hydration water

Optochemical Control of Deoxyoligonucleotide Function via a Nucleobase-Caging Approach

Emissive Synthetic Cofactors: Enzymatic Interconversions of ^tzA Analogues of ATP, NAD⁺, NADH, NADP⁺, and NADPH

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The Chemical Biology of Aptamers: Synthesis and Applications

Cited by 5 publications

References 225 publications

Molecular dynamics simulations of structural and dynamical aspects of DNA hydration water

Molecular dynamics simulations of structural and dynamical aspects of DNA hydration water

Optochemical Control of Deoxyoligonucleotide Function via a Nucleobase-Caging Approach

Emissive Synthetic Cofactors: Enzymatic Interconversions of tzA Analogues of ATP, NAD+, NADH, NADP+, and NADPH

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Emissive Synthetic Cofactors: Enzymatic Interconversions of ^tzA Analogues of ATP, NAD⁺, NADH, NADP⁺, and NADPH