2015
DOI: 10.1186/s40508-015-0028-3
|View full text |Cite
|
Sign up to set email alerts
|

An astute synthesis of locked nucleic acid monomers

Abstract: Novel attributes of Locked Nucleic Acid (LNA) makes it preferable over most of the other classes of modified nucleic acid analogues and therefore, it has been extensively explored in different synthetic oligonucleotide based therapeutics. In addition to five oligonucleotides of this class undergoing clinical trials, a healthy pipeline in pre-clinical studies validates the tenacity of LNA. Due to the increasing demand, an efficient biocatalytic methodology has recently been devised for the convergent synthesis … Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

0
11
0

Year Published

2019
2019
2022
2022

Publication Types

Select...
6

Relationship

0
6

Authors

Journals

citations
Cited by 10 publications
(11 citation statements)
references
References 24 publications
0
11
0
Order By: Relevance
“…The starting compound of this study is a derivative of α-D-ribofuranose known as 3- O -benzyl-4- C -(hydroxymethyl)-1, 2- O -isopropylidene-α-D-ribofuranose which is widely utilized for synthesizing bridged nucleoside analogues ( Hari et al, 2002 , Rahman et al, 2008 , Sharma et al, 2015 ). Chemicals and solvents applied in the synthetic procedures were procured from either Sigma-Aldrich (USA) or Merck (Germany).…”
Section: Methodsmentioning
confidence: 99%
“…The starting compound of this study is a derivative of α-D-ribofuranose known as 3- O -benzyl-4- C -(hydroxymethyl)-1, 2- O -isopropylidene-α-D-ribofuranose which is widely utilized for synthesizing bridged nucleoside analogues ( Hari et al, 2002 , Rahman et al, 2008 , Sharma et al, 2015 ). Chemicals and solvents applied in the synthetic procedures were procured from either Sigma-Aldrich (USA) or Merck (Germany).…”
Section: Methodsmentioning
confidence: 99%
“…Despite their recent success in the oligotherapeutic field, PMOs have several drawbacks: (a) their neutral backbone results in poor cell permeability and requires transfection as cationic dendrimer formulations or as conjugates of cell penetrating peptides (PPMOs) in order to achieve the intended biological effects (b) the chemical synthesis of PMOs has been conventionally carried out using N ‐tritylated 5′‐chlorophosphoramidate morpholino monomers which have poor solution‐phase stability , long condensation times and low stepwise condensation yields , making PMO synthesis relatively expensive. The chemical synthesis of other modifications that confer increased thermal stability to an ODN, such as the conformationally restricted nucleotide analogues (LNA, BNA and tricyclo‐DNA) involve tedious multi‐step organic syntheses (~ 15 steps from precursor to 5’‐DMTrO‐nucleoside phosphoramidite per nucleobase) resulting in lower overall yields, making it more expensive and fairly inaccessible to most laboratories . Thus, there still exists a need for developing ODN modifications which can provide higher hybridization affinity while reducing overall time and costs associated with their synthesis.…”
Section: Methodsmentioning
confidence: 99%
“…solution-phase stability [11], long condensation times and low stepwise condensation yields [12], making PMO synthesis relatively expensive. The chemical synthesis of other modifications that confer increased thermal stability to an ODN, such as the conformationally restricted nucleotide analogues (LNA, BNA and tricyclo-DNA) involve tedious multi-step organic syntheses (~15 steps from precursor to 5'-DMTrOnucleoside phosphoramidite per nucleobase) resulting in lower overall yields, making it more expensive and fairly inaccessible to most laboratories [7,13,14]. Thus, there still exists a need for developing ODN modifications which can provide higher hybridization affinity while reducing overall time and costs associated with their synthesis.…”
mentioning
confidence: 99%
“…190 Moreover, LNA modifications can be incorporated into oligonucleotides by standard solid-phase oligonucleotide synthesis allowing the number of LNA modifications within an oligonucleotide to be varied to tune the hybridisation properties. As a result, LNA modifications have had a major impact in nucleic acid research and biotechnology, 186,189,191 and they are now commercially available. LNAs have found applications in material science, molecular diagnostics and biotechnology, while addressing challenges such as target binding selectivity as well as contributing to enzymatic and chemical stability.…”
Section: Locked Nucleic Acidsmentioning
confidence: 99%
“…26 ). 189 LNAs have strong binding affinity and selectivity for complementary DNA and RNA strands. The greater duplex stability relative to unmodified DNA is reflected in UV melting studies where the addition of a single LNA modification to DNA sequences typically increases the binding affinity towards RNA by around 7 to 8 °C and binding to DNA by around 5 °C.…”
Section: Nucleic Acid Backbone Modificationsmentioning
confidence: 99%