Fraser, William and Walsh, Andrew J. (2025). DNA Triplex-Formation by a Covalent Conjugate of the Anticancer Drug Temozolomide. DNA, 5 (3),
Abstract
Background/Objectives: Temozolomide is an important drug used for the treatment of glioblastoma multiforme. Covalent conjugation of temozolomide to triplex-forming oligonucleotides could facilitate better sequence discrimination when targeted to DNA to lessen off-target effects and potentially reduce side-effects associated with conventional chemotherapy. The base sensitivity of temozolomide precludes use of basic deprotection conditions that typify the solid-supported synthesis of oligonucleotides. Methods: A novel di-iso-propylsilylene-linked solid support was developed and used in solid-supported synthesis of oligonucleotide conjugates. Results: Conditions were established whereby fully deprotected, solid-supported oligonucleotides could be prepared for derivatization. Cleavage of the di-iso-propylsilylene linker was possible using mild, acidic conditions. Conclusions: The di-iso-propylsilylene-linked solid support was developed and shown to be compatible with base-sensitive oligonucleotide conjugate formation. The DNA triplex formation exhibited by a temozolomide oligonucleotide conjugate was equal in stability to the unconjugated control, opening new possibilities for sequence-selective delivery of temozolomide to targeted DNA.
Publication DOI: | https://doi.org/10.3390/dna5030036 |
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Divisions: | College of Health & Life Sciences > Aston Pharmacy School College of Health & Life Sciences |
Funding Information: | This research was funded by Cancer Research UK SP2283/0101. |
Additional Information: | Copyright © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
Uncontrolled Keywords: | anticancer,conjugate,glioblastoma multiforme,oligonucleotide,solid-supported,synthesis,temozolomide,triplex |
Publication ISSN: | 2673-8856 |
Last Modified: | 30 Jul 2025 08:12 |
Date Deposited: | 29 Jul 2025 12:25 |
Full Text Link: | |
Related URLs: |
https://www.mdp ... 673-8856/5/3/36
(Publisher URL) |
PURE Output Type: | Article |
Published Date: | 2025-07-22 |
Accepted Date: | 2025-06-26 |
Authors: |
Fraser, William
(![]() Walsh, Andrew J. |
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