| 摘要 |
FIELD: biotechnology.SUBSTANCE: present invention relates to biotechnology and represents a diabody molecule. Diabody molecule is able to bind to two different epitopes on two different cells, where first epitope is expressed on type of cells different from type of cells on which second epitope is expressed, so that diabody can bring said two cells closer, wherein said diabody contains a first polypeptide chain and a second polypeptide chain covalently bonded to each other. Said first polypeptide chain comprises in direction from N-end to C-end a first domain comprising a binding region of a light chain variable domain of a first immunoglobulin (VL1) specific for a first epitope, second domain comprising a binding region of a heavy chain variable domain of a second immunoglobulin (VH2) specific for a second epitope, and comprising a cysteine domain, wherein said first domain and second domain are covalently bonded by peptide linker of 0-9 amino acid residues so said first domain and second domain are not associated with formation of section binding epitope. Said second polypeptide chain comprises from N-terminal to C-end of third domain containing binding region of a second light chain variable domain of immunoglobulin (VL2), fourth domain containing binding region of a heavy chain variable domain of first immunoglobulin (VH1) comprising a cysteine domain, wherein said third domain and fourth domain are covalently bonded by peptide linker of 0-9 amino acid residues so that said third domain and fourth domain are not associated with formation of an epitope binding portion. First domain and fourth domain are associated with formation of a first binding portion of (VL1)(VH1), which binds first epitope, and second domain and third domain are associated with formation of a second binding portion of (VL2)(VH2), which binds the second epitope. Cysteines comprising cysteine domains of said first and second polypeptide chains are connected together by a disulphide bond; and where said first or second polypeptide chain additionally contains either a divider in form of E-spiral (SEQ ID NO: 299), or divider in form of a K-spiral (SEQ ID NO: 300), which promote heterodimer and are located on C-end relative to said second domain or fourth domain.EFFECT: invention enables to obtain diabody molecules, effective for treating various diseases and disorders, including immunological disorders and malignant tumours.23 cl, 49 dwg, 17 tbl, 19 ex |
