AT-CuAAC Synthesis of Mechanically Interlocked Oligonucleotides

Acevedo‐Jake, Amanda M.; Ball, Andrew T.; Galli, Marzia; Kukwikila, Mikiembo; Denis, Mathieu; Singleton, Daniel; Tavassoli, Ali; Goldup, Stephen M.

doi:10.1021/jacs.0c01670

Cited by 36 publications

(24 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Goldup an co‐workers reported [2]rotaxanes incorporating oligonucleotides as the axle‐component (see Figure 8B) and studied their behavior as primers in PCR [58] . By combining two types of Cu‐catalyzed alkyne‐azide click‐reactions, namely the click‐DNA ligation developed by Tavassoli, Brown and co‐workers [59] and the active metal templated synthesis of rotaxanes, [16] they were able to produce different [2]rotaxanes with oligonucleotide‐axles in excellent yields, with lengths of up to 20 nucleotides.…”

Section: Mims Built From Biomoleculesmentioning

confidence: 99%

Mechanically Interlocked Molecules for Biomedical Applications

Riebe

Niemeyer

2021

Eur J Org Chem

View full text Add to dashboard Cite

Mechanically interlocked molecules (MIMs) carry great potential in different fields of chemistry, based on their specific structures, their internal dynamics, their stimuli‐responsive behavior, and other unique features of the mechanical bond. This minireview presents some of the most recent developments in their use for medical and biological applications. For example, they have been used to influence, enhance or block the action of therapeutic agents to enable targeted drug delivery. The dynamic structural properties have been used to generate switches and transporters, as well as sensors for various medically relevant species. Building MIMs by incorporating biomolecules like DNA and proteins has served as a novel way to control their properties.

show abstract

Section: Mims Built From Biomoleculesmentioning

confidence: 99%

Mechanically Interlocked Molecules for Biomedical Applications

Riebe

Niemeyer

2021

Eur J Org Chem

View full text Add to dashboard Cite

show abstract

“…The intensity of the ECD bands of the rotaxane was slightly higher than those of the axle. Other chiral moieties, such as BINOLs, [20e,90] amino acids, [91] cyclodextrins, [92] oligonucleotides [93] or planar chiral pillar [5]arene macrocycles, [94] were included in the architecture of the rotaxanes and induced a preferential absorption of circularly polarized light. Moreover, the analysis of ECD spectra of a polymer composed of chiral pendant rotaxanes established that incorporating a BINOL unit in the macrocycle led to chirality transfer to the polymer, and therefore, to a preferred helicity of the polymer.…”

Section: Rotaxanes 41 Ecd Spectroscopy Applied To Rotaxanesmentioning

confidence: 99%

Chiroptical Properties of Mechanically Interlocked Molecules

David

Stoddart

2021

Israel Journal of Chemistry

View full text Add to dashboard Cite

Mechanically Interlocked Molecules (MIMs), such as catenanes, knots, and rotaxanes, are a class of molecules that possess mechanical bonds. These bonds constitute an entanglement in space between components of the MIMs that cannot be separated without breaking a participating covalent bond. Although it is possible to synthesize chiral MIMs with covalent stereogenic centers, this new bond opens up the possibilities of axial, planar and helical chirality, as well as topologically chiral compounds. A growing number of chiral MIMs have been investigated and employed in numerous applications, ranging from sensing to catalysis. While the investigation of the properties of MIMs is highly developed, it is also essential to study their chiroptical properties. In this review, we focus on the chiroptical properties of chiral MIMs. We discuss their electronic circular dichroism (ECD) since these properties have been analyzed in some detail in relation to their structures and stereochemistry. Although only a few examples have been described to date, we discuss the encouraging circularly polarized luminescence (CPL) properties of MIMs. The review also includes a recent study of vibrational circular dichroism (VCD) in mechanically planar chiral rotaxanes suggesting that this technique is a promising tool for analyzing the structures of MIMs. The study of the chiroptical properties of MIMs can have a large impact on their use in materials science or as catalysts. One of the key advantage of chiral MIMs is that they provide a means of generating efficient chiroptical switches that have a bright future in the context of multiple applications.

show abstract

“…[18][19][20][21][22] Other examples include the selective delivery of a drug to cancer cells 23 and a recent report wherein encirclement of a biocompatible 1,2,3-triazole linker by a macrocycle inhibited duplex formation of an unnatural DNA strand, supressing its ability to act as a primer for PCR amplification. 24 Herein, we describe the use of rotaxanes to act as triggerable cages for DNA binders as well as to aid their controlled release inside cells. In particular, we have developed a system to selectively target G-quadruplex DNA (G4 DNA), a non-canonical DNA structure formed from guanine-rich sequences which has been implicated in various biological processes including telomeric maintenance, transcription, translation and replication.…”

Section: Introductionmentioning

confidence: 99%

Rotaxanes as Cages to Control DNA Binding, Cytotoxicity, and Cellular Uptake of a Small Molecule**

et al. 2021

View full text Add to dashboard Cite

A wide range of therapies and imaging agents target biomolecules such as DNA and proteins. However, it is often difficult to design drugs and molecular probes with high selectivity for a given target whilst also controlling their cellular permeability and localisation. A biomolecule that has recently attracted significant interest is G-quadruplex DNA, a tetra-stranded nucleic acid structure which has been implicated in telomere maintenance, gene regulation and replication. Herein we report a new approach towards the controlled DNA binding properties and cellular uptake and localisation of a small molecule. More specifically, we report the synthesis of rotaxanes which incorporate as a stoppering unit a known G-quadruplex DNA binder, namely a Pt II-salphen complex. This compound is prevented from interacting with DNA when it is part of the mechanically interlocked assembly. The second rotaxane stopper was designed to be cleaved by either light or the activity of an esterase. In the presence of such stimuli, the rotaxane breaks apart, releasing the Pt II-salphen complex and activating its ability to bind to G-quadruplex DNA. Furthermore, we show that the rotaxanes regulate the cell uptake of this metal complex as well as its cytotoxicity. While the free G-quadruplex DNA binder is not cell permeable (and therefore not cytotoxic), when incorporated in the rotaxane it is readily taken up by cells. The cytotoxicity of the light-triggerable rotaxane in osteosarcoma U2OS cells increases dramatically after the incubated cells were exposed to light. Finally, we show that once the rotaxanes are broken apart inside the cell (either by light or esterases), a significant proportion of the freed G-quadruplex binder localises in the cell nucleus.

show abstract

AT-CuAAC Synthesis of Mechanically Interlocked Oligonucleotides

Abstract: We present a simple strategy for the synthesis of main chain oligonucleotide rotaxanes with precise control over the position of the macrocycle. The novel DNA-based rotaxanes were analyzed to assess the effect of the mechanical bond on their properties.

Cited by 36 publications

References 105 publications

Mechanically Interlocked Molecules for Biomedical Applications

Mechanically Interlocked Molecules for Biomedical Applications

Chiroptical Properties of Mechanically Interlocked Molecules

Rotaxanes as Cages to Control DNA Binding, Cytotoxicity, and Cellular Uptake of a Small Molecule**

Contact Info

Product

Resources

About