Investigating the Activation Kinetics of Phosphoramidites for Oligonucleotide Synthesis

Laraman, Fiona J.; Fisk, Heidi; Whittaker, D.; Cherryman, Janette H.; Diorazio, Louis J.

doi:10.1021/acs.oprd.1c00195

Cited by 3 publications

(4 citation statements)

References 17 publications

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“…Additionally, the length of the hydrophobic carbon chain has a significant contribution in stabilizing the NB3 hydrogel. 49,50 These factors jointly have an important role in the formation of a stable nanofibrous hydrogel.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…The formation of a stronger hydrogel in the presence of monovalent alkali metal ion K + indicates the cation-selective behavior of the NB3 hydrogel. Additionally, the length of the hydrophobic carbon chain has a significant contribution in stabilizing the NB3 hydrogel. , These factors jointly have an important role in the formation of a stable nanofibrous hydrogel.…”

Section: Resultsmentioning

confidence: 99%

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Synthesis and Structural Studies of Nucleobase Functionalized Hydrogels for Controlled Release of Vitamins

Bhowmik,

Ghosh,

Sanghvi

et al. 2023

ACS Appl. Bio Mater.

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The development of biomolecule-derived biocompatible scaffolds for drug delivery applications is an emerging research area. Herein, we have synthesized a series of nucleobase guanine (G) functionalized amino acid conjugates having different chain lengths to study their molecular self-assembly in the hydrogel state. The gelation properties have been induced by the correct choice of chain lengths of fatty acids present in nucleobase functionalized molecules. The effect of alkali metal cations, pH, and the concentration of nucleobase functionalized amino acid conjugates in the molecular self-assembly process has been explored. The presence of Hoogsteen hydrogen bonding interaction drives the formation of a G-quadruplex functionalized hydrogel. The DOSY nuclear magnetic resonance is also performed to evaluate the self-assembling behavior of the newly formed nucleobase functionalized hydrogel. The nanofibrillar morphology is responsible for the formation of a hydrogel, which has been confirmed by various microscopic experiments. The mechanical behaviors of the hydrogel were evaluated by rheological experiments. The in vitro biostability of the synthesized nucleobase amino acid conjugate is also investigated in the presence of hydrolytic enzymes proteinase K and chymotrypsin. Finally, the nucleobase functionalized hydrogel has been used as a drug delivery platform for the control and sustained pH-responsive release of vitamins B2 and B12. This synthesized nucleobase functionalized hydrogel also exhibits noncytotoxic behavior, which has been evaluated by their in vitro cell viability experiment using HEK 293 and MCF-7 cell lines.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Synthesis and Structural Studies of Nucleobase Functionalized Hydrogels for Controlled Release of Vitamins

Bhowmik,

Ghosh,

Sanghvi

et al. 2023

ACS Appl. Bio Mater.

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“…The high demand for new PAT tools is also reflected in the efforts made by various companies to gain more insight into different processes. Recently, AstraZeneca published an article demonstrating the use of in-line mid-IR spectroscopy and rapid NMR spectroscopy as PAT tools to real-time investigate the difference in activation kinetics of two nucleotide structures in SPOS . Likewise, at Novartis, we demonstrated the feasibility of using the refractive index (RI) as a PAT tool to monitor solid-phase peptide synthesis (SPPS) .…”

Section: Introductionmentioning

confidence: 99%

“…Recently, AstraZeneca published an article demonstrating the use of in-line mid-IR spectroscopy and rapid NMR spectroscopy as PAT tools to real-time investigate the difference in activation kinetics of two nucleotide structures in SPOS. 9 Likewise, at Novartis, we demonstrated the feasibility of using the refractive index (RI) as a PAT tool to monitor solid-phase peptide synthesis (SPPS). 10 Due to the similarity of SPPS and SPOS, it was obvious for us to also investigate the potential of RI as a monitoring tool in the latter process.…”

Section: Introductionmentioning

confidence: 99%

Refractive Index to Monitor Solid-Phase Oligonucleotide Synthesis

Heilmann

Ackermann

Lopez

2022

Org. Process Res. Dev.

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Automated solid-phase oligonucleotide synthesis (SPOS) is a highly developed and efficient process, which has been used in academia and industry since decades. Still, some chemical transformations as well as all washing steps are run in a black box modus as only a few process analytical technology tools are available, namely, UV–vis spectroscopy and conductivity. To ensure high yields and efficiencies in each of the numerous steps, the process is usually performed using an excess of building blocks, reagents, and solvents. The reaction conditions are defined according to standard procedures and not necessarily to the real or optimal need of the reaction. As a result, SPOS suffers from generating large amounts of toxic waste, and its reduction is a must from the perspective of sustainability. One approach to make the process more sustainable is to add more complementary monitoring tools that provide online information about the progress of the process. Herein, we disclose our promising preliminary results in the use of refractive index to monitor SPOS.

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