US 12,235,275 B2
Fluorescent substrates for poly(ADP-ribosyl) hydrolases
Paul J. Hergenrother, Champaign, IL (US); and Bryon S. Drown, Champaign, IL (US)
Assigned to The Board of Trustees of the University of Illinois, Urbana, IL (US)
Appl. No. 17/274,395
Filed by The Board of Trustees of the University of Illinois, Urbana, IL (US)
PCT Filed Sep. 9, 2019, PCT No. PCT/US2019/050221
§ 371(c)(1), (2) Date Mar. 8, 2021,
PCT Pub. No. WO2020/055753, PCT Pub. Date Mar. 19, 2020.
Claims priority of provisional application 62/728,955, filed on Sep. 10, 2018.
Prior Publication US 2022/0050112 A1, Feb. 17, 2022
Int. Cl. G01N 33/58 (2006.01); C09K 11/06 (2006.01); G01N 21/64 (2006.01)
CPC G01N 33/582 (2013.01) [C09K 11/06 (2013.01); G01N 21/6428 (2013.01); C09K 2211/1022 (2013.01); C09K 2211/1059 (2013.01); G01N 2021/6439 (2013.01)] 18 Claims
 
1. A compound of Formula I:
AM-L-FS1-PP-FS2-NB  (I),
or a salt thereof;
wherein
AM is an aromatic chromophore (A1):

OG Complex Work Unit Chemistry
wherein
Q1 and Q2 are each independently H, halo, carboxyl, sulfonyl, nitro, aryl, branched or unbranched (C1-C6)alkyl;
Q3 is H or halo;
each X is independently NRA, O, or S; and
RA is H, or branched or unbranched (C1-C6)alkyl; and
n is 1-3;
wherein aryl and each (C1-C6)alkyl are optionally substituted; or
AM is A2:

OG Complex Work Unit Chemistry
wherein
R1 and R2 are each independently halo, carboxyl, sulfonyl, nitro, aryl, branched or unbranched (C1-C6)alkyl;
wherein aryl and (C1-C6)alkyl are optionally substituted; or
AM is an acridine, fluorescein, or quinazoline;
L is a linker: O;

OG Complex Work Unit Chemistry
wherein each J is independently O, —N(C═O)O—, or —O(C═O)O—;
FS1 and FS2 are furanose moieties;
PP is a monophosphate, diphosphate, or triphosphate; and
NB is a nucleobase (N2):

OG Complex Work Unit Chemistry
wherein
R5 is H or N(RB)2; and
each RB is independently H, or branched or unbranched (C1-C6)alkyl;
wherein the C5-carbons of FS1 and FS2 are covalently bonded to PP via a C—O bond, the C1-carbon of FS2 is covalently bonded to NB via a C—N bond, and the C1-carbon of FS1 is covalently bonded to AM via L.