US 12,281,134 B2
Electrochemically-cleavable linkers
Bichlien Nguyen, Seattle, WA (US); Jake Smith, Seattle, WA (US); and Karin Strauss, Seattle, WA (US)
Assigned to MICROSOFT TECHNOLOGY LICENSING, LLC, Redmond, WA (US)
Filed by MICROSOFT TECHNOLOGY LICENSING, LLC, Redmond, WA (US)
Filed on Feb. 4, 2020, as Appl. No. 16/781,987.
Prior Publication US 2021/0238577 A1, Aug. 5, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07H 19/10 (2006.01); C12P 19/34 (2006.01); C12Q 1/6834 (2018.01); C12N 9/12 (2006.01); C12N 9/96 (2006.01)
CPC C07H 19/10 (2013.01) [C12P 19/34 (2013.01); C12Q 1/6834 (2013.01); C12N 9/1264 (2013.01); C12N 9/96 (2013.01); C12Y 207/07031 (2013.01)] 21 Claims
 
1. A compound having a structure P—Y-L1-C1-C2-L2-L3-nucleotide, wherein:
P is a bound group that is a peptide, a linked nucleotide, a fluorophore, or a water-soluble group;
Y is optional, if present Y is a bound group attachment group with the structure:

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 α-S-β, or α-NH2-β, wherein α represents a point of attachment to P and β represents a point of attachment to L1 or C1;
L1 is optional, if present L1 is a flexible extension with the structure one or more of:

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 wherein n is 1-20, R1 is hydrogen or a substituted or unsubstituted straight or branched alkyl group having 1 to 6 carbon atoms, wherein β represents a point of attachment to Y or P and χ represents a point of attachment to C1;
C1 is a cleavable group with the structure:

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 wherein X1 is 1 to 4 ring substituents selected from the group consisting of a hydroxyl group, an ether group with an alkyl group having 1 to 3 carbon atoms, an amine group which is unsubstituted or substituted with one or two alkyl groups having 1 to 2 carbon atoms, an alkyl group having 1 to 2 carbon atoms, and a halogen and X2 is hydrogen, a methyl group, an ethyl group, or an isopropyl group,

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 or

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 wherein x represents a point of attachment to L1, Y, or P and δ represents a point of attachment to C2;
C2 is an extension of C1 with the structure:

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 wherein R2 is hydrogen or a substituted or unsubstituted straight or branched alkyl group having 1 to 6 carbon atoms, δ represents a point of attachment to C1 and ε represents a point of attachment to L2 or L3;
L2 is optional, if present L2 is flexible extension with the structure:

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 wherein n is 1-20, R1 is hydrogen or a substituted or unsubstituted straight or branched alkyl group having 1 to 6 carbon atoms, wherein ε represents a point of attachment to C2 and ϕ represents a point of attachment to L3 and wherein at least one of L1 or L2 is present, and
L3 is a nucleotide attachment group with the structure:

OG Complex Work Unit Chemistry
 wherein ϕ represents a point of attachment to C1, C2, or L2 and γ represents a point of attachment to the nucleotide.