Tellurium-Modified Oligonucleotides for DNA Structure Studies
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Solution Overview
Problem
There is a need for the identification of new Te-nucleoside phosphoramidites and Te-modified oligonucleotides, and their derivatives in DNAs, RNAs, and modified nucleic acids, as well as methods for their synthesis and application in drug discovery and research.
Innovation Solution
The synthesis of Te-nucleoside phosphoramidites and Te-modified oligonucleotides, including the protection of 2'-tellurium functionality for compatibility with solid-phase synthesis, and the exploration of their redox properties to facilitate DNA damage studies and structure investigations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If tellurium functionality is introduced into nucleosides for structural studies, then the ability to investigate DNA structure and function is improved, but the compatibility with solid-phase synthesis and stability during deprotection is worsened
Solution Approach 1:
The patent applies preliminary protection of the tellurium functionality with a benzyl group before solid-phase oligonucleotide synthesis. This protective action is performed in advance to prevent unwanted reactions during synthesis and deprotection steps, thereby maintaining both the versatility for structural studies and the stability required for reliable synthesis
Solution Approach 2:
The patent modifies the chemical state of tellurium by introducing different protective groups (benzyl, p-methoxybenzyl) that can be selectively removed under specific conditions. This parameter change allows the tellurium functionality to remain stable during synthesis while still enabling subsequent structural investigations through controlled deprotection
2Measurement precision
If tellurium is incorporated into nucleosides for site-specific fragmentation studies, then the precision of DNA damage investigation is improved, but the complexity of synthesis and purification is worsened
Solution Approach 1:
The patent uses tellurium-derivatized nucleosides as site-specific markers that enable precise localization of DNA fragmentation events. The tellurium-containing nucleosides act as discrete segments or markers within the oligonucleotide sequence, allowing researchers to precisely identify and study fragmentation sites without complicating the overall synthesis approach
Solution Approach 2:
The tellurium functionality serves as an intermediary marker that links the synthetic oligonucleotide to the fragmentation study. The tellurium atom acts as a mediator that can be tracked and detected, enabling precise measurement of DNA damage while the standard solid-phase synthesis methodology handles the complexity of oligonucleotide construction
Data Source
AI summary
Disclosed are compounds of formula (I), a derivative, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. Also disclosed are methods of preparing compound of formula (I), a derivative, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer. Further disclosed are methods of counducting drug discovery and research comprises applying the compound of formula (I), a derivative, or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or said tautomer in an investigation.