Solid support

Patent metadata

Field	Value
Publication number	US-12258680-B2
Application number	US-201917055733-A
Country	US
Kind code	B2
Filing date	May 17, 2019
Priority date	May 18, 2018
Publication date	Mar 25, 2025
Grant date	Mar 25, 2025

Abstract

A solid support for use in non-aqueous DNA-conjugated molecule reactions, wherein the support comprises a solid body formed from a plurality of polyethylene glycol units, wherein the solid body includes at least one cationic moiety.

First claim

The invention claimed is:

1. A solid support for use in non-aqueous DNA-conjugated molecule reactions, wherein the support comprises a solid body formed from a plurality of polyethylene glycol units, wherein the solid body includes at least one cationic moiety, wherein the cationic moiety includes a quaternary ammonium group or a guanidinium group, and wherein the cationic moiety is a compound according to Formula I:

wherein:
Body is the solid support formed from a plurality of polyethylene glycol units;
R is hydrogen; C 1 -C 8 alkyl optionally substituted by hydroxy, phenyl, C 3 -C 8 cycloalkyl, 5 to 10 membered heterocyclic ring or —OC 1 -C 8 alkyl; C 3 -C 8 cycloalkyl; —C(O)C 1 -C 8 alkyl; or a 5 to 10 membered heterocyclic ring;
X is X 1 or X 2 , wherein
X 1 is a C 1 -C 20 alkylene chain, wherein the chain is straight or branched and is optionally substituted by one or more substituents selected from halogen, —OH, C 1 -C 8 alkoxy, nitro, cyano, —COOH, carbamoyl, —N(R 4 )R 5 , C 3 -C 6 cycloalkyl, 3 to 7 membered heterocyclic ring, phenyl, 5 or 6 membered heteroaryl, or C 1 -C 4 alkyl-phenyl;
X 2 is —Z—X 1 —
wherein Z is selected from —(CH 2 ) a —R x —(CH 2 ) a —NH—C(═O)—; —(CH 2 ) a —CH((CH 2 ) a —R x1 )NH—C(═O)—; —(CH 2 ) a —(O) 0-1 —R x2 —CH(R x3 )NH—C(═O)—; and —(CH 2 ) b —(O) 0-1 —(CH 2 ) b —NH—C(═O)—;
a is an integer from 0 to 6;
b is an integer from 1 to 6;
R x is selected from phenyl; C 3 -C 8 cycloalkylene; —C(H) 2-x ((C 1 -C 6 alkyl) x )-; naphthyl; and anthracyl,
which phenyl, C 3 -C 8 cycloalkylene, C 1 -C 6 alkyl, naphthyl or anthracyl are optionally substituted 1, 2, 3 or 4 times independently with C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl or halo;

R x1 is selected from phenyl; C 3 -C 8 cycloalkyl; naphthyl; and anthracyl,
which phenyl, C 3 -C 8 cycloalkyl, naphthyl or anthracyl are optionally substituted 1, 2, 3 or 4 times independently with C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl or halo;

R x2 is selected from phenyl; C 3 -C 8 cycloalkylene; naphthyl; and anthracyl,
which phenyl, C 3 -C 8 cycloalkylene, naphthyl or anthracyl are optionally substituted 1, 2, 3 or 4 times independently with C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl or halo;

R x3 is selected from hydrogen; phenyl; and C 3 -C 6 cycloalkyl,
which phenyl or C 3 -C 6 cycloalkyl are optionally substituted 1, 2, 3 or 4 times independently with C 1 -C 6 alkyl; C 1 -C 6 alkoxy; C 1 -C 6 haloalkyl or halo;

x is an integer from 0 to 2;
Y is C(O); and
R 1 , R 2 , R 3 are each independently selected from hydroxy; C 1 -C 8 alkyl optionally substituted by hydroxy, phenyl, C 3 -C 8 cycloalkyl, 5 to 10 membered heterocyclic ring or —OC 1 -C 8 alkyl; C 3 -C 8 cycloalkyl; —C(O)C 1 -C 8 alkyl; or a 5 to 10 membered heterocyclic ring;
R 4 and R 5 are each independently selected from hydrogen; hydroxy; C 1 -C 8 alkyl optionally substituted by hydroxy, phenyl, C 3 -C 8 cycloalkyl, 5 to 10 membered heterocyclic ring or —OC 1 -C 8 alkyl; C 3 -C 8 cycloalkyl; —C(O)C 1 -C 8 alkyl; or a 5 to 10 membered heterocyclic ring.

2. The solid support according to claim 1 , wherein
R 1 , R 2 , R 3 , R 4 and R 5 are each independently selected from C 1 -C 8 alkyl optionally substituted by phenyl or C 3 -C 8 cycloalkyl; or C 3 -C 8 cycloalkyl.

3. The solid support according to claim 1 , wherein X 1 is a C 1 -C 20 alkylene chain wherein the chain is straight or branched and is unsubstituted.

4. The solid support according to claim 3 , wherein X 1 is a C 1 -C 10 alkylene chain wherein the chain is straight and is unsubstituted.

5. The solid support according to claim 1 , wherein R is H.

6. The solid support according to claim 1 , wherein R 1 , R 2 and R 3 are each independently a C 1 -C 6 alkyl.

7. The solid support according to claim 6 , wherein R 1 , R 2 and R 3 are the same.

8. The solid support according to claim 7 , wherein R 1 , R 2 and R 3 are each methyl.

9. The solid support according to claim 1 , wherein R 4 and R 5 are each independently selected from hydrogen and a C 1 -C 6 alkyl.

10. The solid support according to claim 1 , wherein the solid body is formed from a cross-linked polyethylene glycol polymer.

11. The solid support according to claim 1 , wherein the solid body is formed from the NovaPEG resin of formula (IV)

PEGA resin of formula (V)

or the TentaGel resin of formula (VI).

12. The solid support according to claim 11 , wherein the solid body is formed from the NovaPEG resin of formula (IV).

13. A method of reacting a DNA-conjugated compound using one or more non-aqueous solvents, wherein the method includes the steps of:
i) adsorbing the DNA-conjugated compound onto a solid support as defined in claim 1 ; and
ii) reacting the supported DNA-conjugated compound with a reagent in a non-aqueous solvent system.

Assignees

• Novartis Ag

Inventors

• Berst Frederic
• Ruff Yves

Classifications

• G01N33/545

  Synthetic resin · CPC title

• C07C237/12

  having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups (peptides C07K) · CPC title

• C07B2200/11

  Compounds covalently bound to a solid support · CPC title

• C07C2601/14

  The ring being saturated · CPC title

• C40B20/04

  Identifying library members by means of a tag, label, or other readable or detectable entity associated with the library members, e.g. decoding processes · CPC title