| 主权项 |
1. A linker unit comprising a center core, a plurality of linking arms, a plurality of first elements, and optionally a coupling arm, wherein
the center core 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 integer from 2 to 15; the plurality of linking arms are respectively linked to the K residues of the center core; the plurality of first elements are respectively linked to the plurality of linking arms via forming an amide bond therebetween, or via thiol-maleimide reaction, copper catalyzed azide-alkyne cycloaddition (CuAAC) reaction, strained-promoted azide-alkyne click chemistry (SPAAC) reaction, or inverse electron demand Diels-Alder (iEDDA) reaction, wherein each of the first elements is an single-chain variable fragment (scFv) specific for fibrin; and 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 thiol group of the cysteine residue is linked with the coupling arm having an azide, an alkyne, a tetrazine, a cyclooctene, or a cyclooctyne group at the free terminus of the coupling arm, wherein, when the plurality of first elements are respectively linked to the plurality of linking arms via CuAAC 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 first elements are respectively linked to the plurality of linking arms 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. |
