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The multivalent G-quadruplex (G4)-ligands MultiTASQs allow for versatile click chemistry-based investigations.

ABSTRACT: Chemical biology hinges on multivalent molecular tools that can specifically interrogate and/or manipulate cellular circuitries from the inside. The success of many of these approaches relies on molecular tools that make it possible to visualize biological targets in cells and then isolate them for identification purposes. To this end, click chemistry has become in just a few years a vital tool in offering practically convenient solutions to address highly complicated biological questions. We report here on two clickable molecular tools, the biomimetic G-quadruplex (G4) ligands MultiTASQ and ^azMultiTASQ, which benefit from the versatility of two types of bioorthogonal chemistry, CuAAC and SPAAC (the discovery of which was very recently awarded the Nobel Prize of chemistry). These two MultiTASQs are used here to both visualize G4s in and identify G4s from human cells. To this end, we developed click chemo-precipitation of G-quadruplexes (G4-click-CP) and in situ G4 click imaging protocols, which provide unique insights into G4 biology in a straightforward and reliable manner.

SUBMITTER: Rota Sperti F

PROVIDER: S-EPMC10320843 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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The multivalent G-quadruplex (G4)-ligands MultiTASQs allow for versatile click chemistry-based investigations.

Rota Sperti Francesco F Mitteaux Jérémie J Zell Joanna J Pipier Angélique A Valverde Ibai E IE Monchaud David D

RSC chemical biology 20230516 7

Chemical biology hinges on multivalent molecular tools that can specifically interrogate and/or manipulate cellular circuitries from the inside. The success of many of these approaches relies on molecular tools that make it possible to visualize biological targets in cells and then isolate them for identification purposes. To this end, click chemistry has become in just a few years a vital tool in offering practically convenient solutions to address highly complicated biological questions. We re ...[more]

PMID: 37415864

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Project description:Albumin is one of the most attractive nanoplatforms for targeted imaging and drug delivery due to its biocompatibility and long circulation half-life. However, previously reported albumin-based nanoplatforms have shown inconsistent blood circulation half-life according to the modified methods, and the affecting factors were not well evaluated, which could hamper the clinical translation of albumin-based nanoplatforms. Herein, we developed a finely tuned click-chemistry based albumin nanoplatform (CAN) with a longer circulation half-life and an efficient tumor targeting ability. Methods: CAN was synthesized in two steps. First, albumin was conjugated with ADIBO-NHS (albumin-ADIBO) by reacting albumin with various molar ratios of ADIBO. The number of attached ADIBO moieties was determined using matrix-assisted laser desorption ionization time of flight (MALDI-TOF). Second, the desired modalities including azide-functionalized chelator, a fluorescence dye, and folate were incorporated into albumin-ADIBO using strain-promoted alkyne-azide cycloaddition reaction (SPAAC reaction). The biodistribution and targeting efficiency of functionalized CANs were demonstrated in mice. Results: The degree of functionalization (DOF) and resulting in vivo biodistribution was controlled precisely using the click chemistry approach. Specifically, the numbers of attached azadibenzocyclooctyne (ADIBO) moieties on albumin, the DOF, were optimized by reacting albumin with varying molar ratios of ADIBO with a high reproducibility. Furthermore, we developed a simple and efficient method to estimate the DOF using UV-visible spectrophotometry (UV-vis), which was further validated by matrix-assisted laser desorption ionization time of flight (MALDI-TOF). The biodistribution of CAN could be controlled by DOF, and CAN with an optimized DOF showed a long circulation half-life (> 18 h). CAN was further functionalized using a simple click chemistry reaction with an azide functionalized chelator, a fluorescence dye, and folate. 64Cu- and folate-labeled CAN (64Cu-CAN-FA) showed effective and specific folate receptor targeting in vivo, with an over two-fold higher uptake than the liver at 24 h post-injection. Conclusions: Our development from the precisely controlled DOF demonstrates that an optimized CAN can be used as a multifunctional nanoplatform to obtain a longer half-life with radioisotopes and ligands, and provides an effective method for the development of albumin-based tumor theranostic agents.

Dataset Information

The multivalent G-quadruplex (G4)-ligands MultiTASQs allow for versatile click chemistry-based investigations.

Publications

The multivalent G-quadruplex (G4)-ligands MultiTASQs allow for versatile click chemistry-based investigations.

Similar Datasets

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