On-oligonucleotide olefin metathesis in water
Researchers have achieved a significant breakthrough in synthetic chemistry by successfully performing ring-closing metathesis (RCM) on oligonucleotide-conjugated systems in neat water. Published in Nature Communications, this study addresses the long-standing challenge of incompatibility between olefin metathesis catalysts and nucleic acids. The team utilized a specially designed anionic, water-soluble ruthenium catalyst to synthesize nucleic acid-tagged macrocycles. This method demonstrates high compatibility with various oligonucleotide tags, including DNA, RNA, and chemically stabilized DNA congeners, resulting in useful conversion rates and effective recovery of the nucleic acids. This advancement unlocks the potential of encoded libraries of synthetic macrocycles for large-scale screening, particularly for targeting conventionally undruggable proteins. By enabling RCM in aqueous environments, the research paves the way for broader applications in drug discovery, including the development of RNA-oligonucleotide therapies. The work represents a critical step forward in combining combinatorial library technologies with robust synthetic methodologies, potentially accelerating the identification of novel therapeutic candidates.
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On-oligonucleotide olefin metathesis in water
Researchers have achieved a significant breakthrough in synthetic chemistry by successfully performing ring-closing metathesis (RCM) on oligonucleotide-conjugated systems in neat water. Published in Nature Communications, this study addresses the long-standing challenge of incompatibility between olefin metathesis catalysts and nucleic acids. The team utilized a specially designed anionic, water-soluble ruthenium catalyst to synthesize nucleic acid-tagged macrocycles. This method demonstrates high compatibility with various oligonucleotide tags, including DNA, RNA, and chemically stabilized DNA congeners, resulting in useful conversion rates and effective recovery of the nucleic acids. This advancement unlocks the potential of encoded libraries of synthetic macrocycles for large-scale screening, particularly for targeting conventionally undruggable proteins. By enabling RCM in aqueous environments, the research paves the way for broader applications in drug discovery, including the development of RNA-oligonucleotide therapies. The work represents a critical step forward in combining combinatorial library technologies with robust synthetic methodologies, potentially accelerating the identification of novel therapeutic candidates.
Nature Communications