| 主权项 |
1. A linker unit comprising,
a center core that comprises, (1) a first polypeptide comprising a plurality of lysine (K) residues, wherein each K residue and its next K residue are separated by a filler sequence comprising glycine (G) and serine (S) residues, and the number of K residues ranges from 2 to 15; or (2) a second polypeptide comprising the sequence of (Xaa—K)n, where Xaa is a PEGylated amino acid having 2 to 12 repeats of ethylene glycol (EG) unit, and n is an integral from 2 to 15; wherein at least one of the N- and C-terminal amino acid residues of the center core is an amino acid having an azide or an alkyne group or is a cysteine residue, wherein when one of the N- and C-terminal amino acid residues is the cysteine residue, the linker unit further comprises, optionally, a coupling arm that is linked to the cysteine residue via the thiol group of the cysteine residue and has the azide, the alkyne, a tetrazine, a cyclooctene, or a cyclooctyne group at the free terminus thereof, a plurality of linking arms respectively linked to the K residues of the center core; optionally, a plurality of connecting arms respectively linked to the plurality of the linking arms via CuAAC reaction, SPAAC reaction, or iEDDA reaction; and a plurality of first elements that are respectively linked to the plurality of linking arms via forming an amide bound therebetween, or via thiol-maleimide reaction, CuAAC reaction, SPAAC reaction, or iEDDA reaction; or respectively linked to the plurality of connecting arms via forming an amide bound therebetween, or via thiol-maleimide reaction, wherein, each of the first elements is fingolimod, fingolimod phosphate, interferon-β, or a single-chain variable fragment (scFv) specific for integrin-α4 or β-amyloid; and when the plurality of linking arms are linked to the plurality of connecting arms or the plurality of first elements via CuAAC reaction or SPAAC reaction, then the amino acid residue at the N- or C-terminus of the center core is a cysteine residue, and the free terminus of the coupling arm is the tetrazine or the cyclooctene group; or when the plurality of linking arms are linked to the plurality of connecting arms or the plurality of first elements via iEDDA reaction, then the amino acid residue at the N- or C-terminus of the center core has the azide or the alkyne group, or the amino acid residue at the N- or C-terminus of the center core is a cysteine residue, and the free terminus of the coupling arm is the azide, the alkyne, or the cyclooctyne group. |
