Dynamic combinatorial library based on pseudopeptides and its use for the detection of cysteine and other biothiols

Patent metadata

Field	Value
Publication number	US-11905236-B2
Application number	US-201917042667-A
Country	US
Kind code	B2
Filing date	Apr 4, 2019
Priority date	Apr 4, 2018
Publication date	Feb 20, 2024
Grant date	Feb 20, 2024

Abstract

The present invention relates to a dynamic chemical network that mimics the transfer of information and ultimately produces a chemical response, for example a readable signal. More specifically, the invention discloses a dynamic system able to selectively sense a biologically-relevant analyte, such as cysteine, in its reduced or its oxidized form (cystine) in aqueous media and in a biofluid (such as urine) for diagnostic application. Due to this property, said dynamic system is useful for the detection of cysteine or its derivatives in biological fluids such as urine.

First claim

The invention claimed is:

1. A mixture of molecules comprising at least a compound as defined by formula (I):

or an isomer or a salt thereof, wherein:
Ra and Rb are independently selected from H, —CONRR′, —COOR, —NRR′, —OH, —C(NH)NH 2 , —CH(OH)CH 3 , aryl-(C 6 -C 10 ) or heteroaryl-(C 6 -C 10 );
R and R′ are independently selected from H or alkyl-(C 1 -C 5 );
m is an integer selected from 0, 1, 2, 3 or 4;
n is an integer selected from 1 or 2;

at least a compound of formula (II):

or an isomer or a salt thereof, wherein:
n′ is an integer selected from 1 or 2;
and at least a compound of formula (III):

or an isomer or a salt thereof, wherein:
Rc represents an aromatic chromophore;
Y is selected from NHCO or CONH;
Z is selected from H, —NH 2 , —OH or —COOH;
p is an integer selected from 0, 1, 2 or 3.

2. The mixture of molecules according to claim 1 , which also comprises at least a compound of formula (IV):

or an isomer or a salt thereof, wherein:
Rd is selected from H or S(CH 2 )qCH(NH 2 )COOH;
q is an integer selected from 1, 2 or 3.

3. The mixture of molecules according to claim 1 , wherein m is 1 and n is 1.

4. The mixture of molecules according to claim 1 , wherein Ra is CONH 2 .

5. The mixture of molecules according to claim 1 , wherein Rb is CONH 2 .

6. The mixture of molecules according to claim 1 , wherein n′ is 1.

7. The mixture of molecules according to claim 1 , wherein Rc is selected from the following chromophores:

8. The mixture of molecules according to claim 1 , wherein Y is —NHCO.

9. The mixture of molecules according to claim 1 , wherein Z is —NH 2 .

10. The mixture of molecules according to claim 1 , wherein p is 1.

11. The mixture of molecules according to claim 1 , wherein Rd is H.

12. The mixture of molecules according to claim 1 , wherein q is 1.

13. A dynamic combinatorial library comprising the mixture of molecules claim 1 .

14. An in vitro method for the detection of a compound of formula (IV):

or an isomer or a salt thereof, wherein:
Rd is selected from H or S(CH 2 )qCH(NH 2 )COOH;

q is an integer selected from 1, 2 or 3
in a sample comprising the following steps:
a) mixing at least a compound of formula (I) with at least a compound of formula (II) and at least a compound of formula (III) according to claim 1 ;
b) contacting the sample comprising the compound of formula (IV) with the mixture of step (a);
c) measuring the fluorescence emission of the mixture obtained in step (b);
d) detecting a significant deviation from a standard; and
e) assigning the sample to the group of samples comprising a compound of formula (IV) when a significant difference has been detected in stage (d).

15. The method according to claim 14 , wherein the molecule of formula (IV) is selected from cysteine or cystine.

16. A kit for the detection of a compound of formula (IV) in a sample of

or an isomer or a salt thereof, wherein:
Rd is selected from H or S(CH 2 )qCH(NH 2 )COOH;

q is an integer selected from 1, 2 or 3,
comprising a mixture of compounds of formula (I), (II) and (III) as described in claim 1 .

Assignees

• Consejo Superior Investigacion

Inventors

• Alfonso Rodriguez Igancio
• Sola Oller Jordi
• Lafuente Fabra Maria

Classifications

• C07C321/06 Primary

  of a saturated carbon skeleton containing rings · CPC title

• G01N33/582

  with fluorescent label · CPC title

• G01N33/6815 Primary

  containing sulfur, e.g. cysteine, cystine, methionine, homocysteine · CPC title

• G01N33/493

  urine · CPC title