Immune receptor modifier conjugate and preparation method and use thereof, coupling precursor for preparing same, and compound for synthesizing coupling precursor
Disclosed is an immune receptor modifier conjugate, obtained from the reaction between a coupling precursor and a biotic ligand, the coupling precursor being a 9-position aminomethyl benzyl purine biotic coupling precursor, and the biotic ligand being selected from one or more of polypeptide, protein, glycoprotein, polysaccharide, polynucleotide, inactivated cells and inactivated microbes. The immune receptor modifier couplet can be used for immunomodulation, antibody preparation, anti-virus, diabetes, tumor immunomodulation, and tumor bio-immunotherapy. The conjugate compounds or salts thereof can be prepared into various therapeutic drugs, and can be prepared into a compound drug together with other drugs, or pharmaceutically acceptable carrier composites or conjugates. Also disclosed are compounds for synthesizing the coupling precursor and salts thereof.
1. An immune receptor modifier conjugate, wherein the conjugate is obtained by the reaction between a coupling precursor and a biotic ligand, and is a compound of formula (I):
wherein R 2 is the biotic ligand, X 1 is OH or SH, R 1 is linear alkyl, branched alkyl, substituted alkyl, unsubstituted alkyl or alkoxyalkyl, X 2 is
or
or
and m and n each are an integer selected from 1 to 10;
When the coupling precursor is a compound of formula 1:
X 2 is the group thiocarbonyl
When the coupling precursor is a compound of formula 2:
X 2 is the group
When the coupling precursor is a compound of formula 3:
X 2 is the group
in which u is an integer selected from 0 to 12; or
When the coupling precursor is a compound of formula 4:
X 2 is the group
in which PEG is a polyethylene glycol group.
2. The immune receptor modifier conjugate of claim 1 , wherein the biotic ligand is one or more selected from the group consisting of polypeptide, protein, glycoprotein, polysaccharide, polynucleotide, inactivated cells and inactivated microorganisms.
3. The immune receptor modifier conjugate of claim 1 , wherein the conjugate comprises the compounds of formulae 1-1, 1-2, 1-3 and 2-1:
4. The immune receptor modifier conjugate of claim 1 , wherein the conjugate comprises:
wherein the biotic ligand R 2 is polypeptide or protein;
MUC1
R 2
NANOG
(epitope)
MG7
POSTN
Twist
Anxa1
Akt1
CD47
Sp17
Conjugate
5-3
5-4
5-5
5-6
5-7
5-8
5-9
5-10
5-11
Molecular
36326
3396
1272
88132
22233
40420
50724
36067
18259
weight
Coupling
4
1
1
5
3
4
6
2
2
degree
MMP-
R 2
PSMA
M2e
NP 366-374
SGLT2
PEAK1
HER2
10
PD-L1
PD-1
Conjugate
5-12
5-13
5-14
5-15
5-16
5-17
5-18
5-19
5-20
Molecular
86890
3357
1424
75029
194385
140469
55430
35834
33353
weight
Coupling
6
1
1
5
3
6
3
6
4.
degree.
5. The immune receptor modifier conjugate of claim 2 , wherein the conjugate comprises the compounds of formulae 1-1, 1-2, 1-3 and 2-1:
6. The immune receptor modifier conjugate of claim 2 , wherein the conjugate comprises:
wherein the biotic ligand R 2 is polypeptide or protein;
MUC1
R 2
NANOG
(epitope)
MG7
POSTN
Twist
Anxa1
Akt1
CD47
Sp17
Conjugate
5-3
5-4
5-5
5-6
5-7
5-8
5-9
5-10
5-11
Molecular
36326
3396
1272
88132
22233
40420
50724
36067
18259
weight
Coupling
4
1
1
5
3
4
6
2
2
degree
MMP-
R 2
PSMA
M2e
NP 366-374
SGLT2
PEAK1
HER2
10
PD-L1
PD-1
Conjugate
5-12
5-13
5-14
5-15
5-16
5-17
5-18
5-19
5-20
Molecular
86890
3357
1424
75029
194385
140469
55430
35834
33353
weight
Coupling
6
1
1
5
3
6
3
6
4.
degree.
7. The immune receptor modifier conjugate of claim 1 , wherein the coupling precursor is a compound of formula 3, and wherein the coupling precursor is a synthesis reaction product of a compound of formula 10:
and