13 research outputs found
Synthetic Strategies and Parameters Involved in the Synthesis of Oligodeoxyribonucleotides According to the Phosphoramidite Method
The phosphoramidite approach has had a major impact on the synthesis of oligonucleotides. This unit describes parameters that affect the performance of this method for preparing oligodeoxyribonucleotides, as well as a number of compatible strategies. Milestones that led to the discovery of the approach are chronologically reported. Alternate strategies are also described to underscore the versatility by which these synthons can be obtained. Mechanisms of deoxyribonucleoside phosphoramidite activation, factors affecting condensation, and deprotection strategies are discussed.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143633/1/cpnc0303.pd
Thiomorpholino oligonucleotides as a robust class of next generation platforms for alternate mRNA splicing
Recent advances in drug development have seen numerous successful clinical translations using synthetic antisense oligonucleotides (ASOs). However, major obstacles, such as challenging large-scale production, toxicity, localization of oligonucleotides in specific cellular compartments or tissues, and the high cost of treatment, need to be addressed. Thiomorpholino oligonucleotides (TMOs) are a recently developed novel nucleic acid analog that may potentially address these issues. TMOs are composed of a morpholino nucleoside joined by thiophosphoramidate internucleotide linkages. Unlike phosphorodiamidate morpholino oligomers (PMOs) that are currently used in various splice-switching ASO drugs, TMOs can be synthesized using solid-phase oligonucleotide synthesis methodologies. In this study, we synthesized various TMOs and evaluated their efficacy to induce exon skipping in a Duchenne muscular dystrophy (DMD) in vitro model using H2K mdx mouse myotubes. Our experiments demonstrated that TMOs can efficiently internalize and induce excellent exon 23 skipping potency compared with a conventional PMO control and other widely used nucleotide analogs, such as 2â˛-O-methyl and 2â˛-O-methoxyethyl ASOs. Notably, TMOs performed well at low concentrations (5â20 nM). Therefore, the dosages can be minimized, which may improve the drug safety profile. Based on the present study, we propose that TMOs represent a new, promising class of nucleic acid analogs for future oligonucleotide therapeutic development
Synthetic Strategies and Parameters Involved in the Synthesis of Oligodeoxyribonucleotides According to the Phosphoramidite Method
Studies on gene control regions. VI. The 5- methyl of thymine, a lac repressor recognition site
Protection of 5â˛âHydroxy Functions of Nucleosides
The 5âhydroxy group is the primary hydroxy group of nucleosides. It is mandatory to protect 5âhydroxyls in all methods of oligonucleotide synthesis that require nucleoside synthons. This unit discusses a wide variety of acidâlabile and baseâlabile protecting groups, as well as enzymatic methods for 5âprotection and deprotection.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143732/1/cpnc0203.pd