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US 2025/0320488 A1Published application
Methods of preparing oligonucleotide-directed combinatorial libraries
AssigneeInsitro, Inc.
InventorsDivya KANICHAR, Richard Edward WATTS, Spurti Umesh AKKI
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Abstract
The present disclosure relates to precursor molecules of DNA-encoded compounds, and methods of preparing thereof. In some aspects, provided herein are methods of synthesizing DNA-encoded compounds, and libraries thereof, from precursor molecules and positional building blocks.
Claims20
A method of synthesizing a DNA-encoded compound comprising an initial building block and at least one positional building block, the method comprising:
- (1) forming a precursor molecule, wherein the precursor molecule comprises a DNA oligonucleotide comprising the initial building block at or near its 5′ terminus, wherein forming the precursor molecule comprises:
- (a) providing a charged carrier, wherein the charged carrier comprises the initial building block and an oligonucleotide sequence comprising a complementary region that is complementary to a portion on an RNA molecule, wherein the oligonucleotide sequence comprising the complementary region comprises a codon that identifies the initial building block,
- (b) hybridizing the complementary region of the charged carrier to the RNA molecule,
- (c) reverse transcribing the RNA molecule that is primed by the charged carrier to form a DNA-RNA heteroduplex, and
- (d) performing RNA hydrolysis on the DNA-RNA heteroduplex to form the precursor molecule;
- and
- (2) synthesizing the DNA-encoded compound using the precursor molecule and the at least one positional building block.
4 more elements
A method of synthesizing a DNA-encoded compound comprising an initial building block and at least one positional building block, the method comprising:
- (1) forming a precursor molecule, wherein the precursor molecule comprises a DNA oligonucleotide comprising the initial building block at or near its 5′ terminus, wherein forming the precursor molecule comprises:
- (a) providing an uncharged carrier, wherein the uncharged carrier comprises a reactive moiety and an oligonucleotide sequence comprising a complementary region that is complementary to a portion on an RNA molecule, wherein the oligonucleotide sequence comprising the complementary region comprises a codon that identifies the initial building block,
- (b) hybridizing the complementary region of the uncharged carrier to the RNA molecule,
- (c) reverse transcribing the RNA molecule primed by the uncharged carrier to form a DNA-RNA heteroduplex,
- (d) performing RNA hydrolysis on the DNA-RNA heteroduplex to form a DNA molecule comprising the reactive moiety, and
- (e) reacting the reactive moiety with the initial building block to form the precursor molecule;
- and
- (2) synthesizing the DNA-encoded compound using the precursor molecule and the at least one positional building block.
5 more elements
Dependencies are inferred from the claim text.