US 12,215,121 B2
Linker structures with minimal scar for enzymatic synthesis
Bichlien Hoang Nguyen, Seattle, WA (US); and Jake Smith, Seattle, WA (US)
Assigned to MICROSOFT TECHNOLOGY LICENSING, LLC, Redmond, WA (US)
Filed by MICROSOFT TECHNOLOGY LICENSING, LLC, Redmond, WA (US)
Filed on Jan. 20, 2023, as Appl. No. 18/157,449.
Application 18/157,449 is a division of application No. 17/162,546, filed on Jan. 29, 2021, granted, now 11,591,361.
Claims priority of provisional application 63/131,700, filed on Dec. 29, 2020.
Prior Publication US 2023/0151047 A1, May 18, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07H 19/10 (2006.01); C25B 3/05 (2021.01); C25B 3/20 (2021.01)
CPC C07H 19/10 (2013.01) [C25B 3/05 (2021.01); C25B 3/20 (2021.01)] 20 Claims
 
1. A compound having a structure Y-L1-C1-L3-nucleotide, wherein:
Y is a bound group attachment group with the structure

OG Complex Work Unit Chemistry
α-S-β, or α-NH2-β, wherein a represents a point of attachment to a bound group and β represents a point of attachment to L1;
L1 is a flexible extension with one or more of the structures:

OG Complex Work Unit Chemistry
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 either Y or C1 and χ represents a point of attachment to the other of Y or C1;
C1 is a cleavable group with the structure:

OG Complex Work Unit Chemistry
wherein X1 is 1 to 4 ring substituents selected from the group consisting of a hydrogen, 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;
X2 is hydrogen, a methyl group, an ethyl group, or an isopropyl group;
R3 is a tert-butyl, allyl, benzyl, methoxybenzyl, dimethoxybenzyl, trimethoxybenzyl, nitrobenzyl, fluorenylmethoxycarbonyl, cyanoethyl, or trichloroethyl group;
R4 and R5 are both separately hydrogen or gem dimethyl or a substituted or unsubstituted straight or branched alkyl group having 1 to 6 carbon atoms; and
R6 is hydrogen or a substituted or unsubstituted straight or branched alkyl group having 1 to 6 carbon atoms, wherein δ represents a point of attachment to L3; and
L3 is a nucleotide attachment group with the structure:

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