Site-specific antibody conjugation and antibody-drug conjugate as specific embodiment thereof
The present invention relates to technology capable of labeling a certain site of an antibody with a certain number of chemical functional groups or cargo moieties. The present invention may provide an antibody product having high uniformity. The present invention may provide an antibody product whose antibody functions are not degraded. That is, the present invention may provide an antibody product whose antibody binding affinity and half-life are not degraded. The present invention is of great significance as being the first technology allowing site-specific labeling of an antibody without any complicated processes.
1 . A peptide-compound conjugate having a structure of formula 6-3:
D-C-A-W-H-(Xa 1 )′-G-E-L-V—W-C-T (SEQ ID NO: 16), [formula 6-3]
wherein,
D is an aspartic acid residue, C is a cysteine residue, A is an alanine residue, W is a tryptophan residue, H is a histidine residue, G is a glycine residue, E is a glutamic acid residue, L is a leucine residue, V is a valine residue, and T is a threonine residue, and
(Xa 1 )′ is
wherein
H 1 is a click chemistry functional group selected from the group consisting of a terminal alkyne, an azide, a strained alkyne, a diene, a dienophile, a dibenzocyclooctyne-amine, a trans-cyclooctene, a norbornene, an alkene, a thiol, and a tetrazine,
D 1 is selected from a covalent bond, C 1-4 alkylene or heteroalkylene, C 2-4 alkenylene, C 2-4 alkynylene, and C 3-8 cycloalkylene,
X 1 is S,
D 2 is selected from C 1-7 alkylene, C 2-7 alkenylene, C 2-7 alkynylene, and C 3-8 cycloalkylene,
D 3 is a covalent bond, or C 1-3 alkylene, and
X 3 is NH,
wherein the peptide exhibits the activity of binding to human immunoglobulin G (IgG), and
wherein the cysteine residue adjacent to the N-terminus of formula 6-3 and the cysteine residue adjacent to the C-terminus of formula 6-3 are optionally linked.
2 . The peptide-compound conjugate according to claim 1 ,
wherein D 1 is a covalent bond and D 2 is methylene.
3 . The peptide-compound conjugate according to claim 1 , wherein D 1 is selected from a covalent bond and —(CH 2 ) 1-4 —.
4 . The peptide-compound conjugate according to claim 1 , wherein D 1 comprises at least one heteroatom.
5 . The peptide-compound conjugate according to claim 1 , wherein D 2 is —CH 2 —.
6 . The peptide-compound conjugate according to claim 1 , wherein D 3 is selected from a covalent bond and —(CH 2 ) 1-3 —.
7 . The peptide-compound conjugate according to claim 1 , wherein D 1 is —CH 2 OCH 2 —.
8 . The peptide-compound conjugate according to claim 1 , wherein D 1 is —CH 2 CH 2 OCH 2 —.
9 . The peptide-compound conjugate according to claim 1 , wherein a moiety comprising polyethylene glycol (PEG) is linked to a N-terminal amine group of the aspartic acid residue.
10 . The peptide-compound conjugate according to claim 1 , wherein a moiety represented by the following structure is linked to a N-terminal amine group of the aspartic acid residue:
11 . The peptide-compound conjugate of claim 1 , wherein the peptide-compound conjugate is represented by any one selected from the following structures:
12 . The peptide-compound conjugate of claim 1 , wherein the peptide-compound conjugate is represented by the following structure: