| 摘要 |
FIELD: medicine, pharmaceutics.SUBSTANCE: invention relates to field of biotechnology, namely to muteins of human tear lipocalin, and can be used in medicine. Mutein of human tear lipocalin (hTLc) has identifiable affinity of binding with human receptor Met (c-Met) receptor tyrosine kinase, or its domain, or fragment of human c-Met. Mutein contains from 6 to 18 amino acid substitutions relative to amino acid sequence of mature lipocalin of human tear liquid (SWISSPROT DATABANK ENTRY P31025; SEQ ID NO:36), selected from group, consisting of Arg 26?Thr, Val, Pro, Ser, Gly; Glu 27?Gln, Gly, Val, Ser; Phe 28?Met, Asp; Pro 29?Leu, Ile, Ala, Trp; Glu 30?Leu, Gly, Arg, Phe; Met 31?Ser; Asn 32?Leu, Arg, Val, Gln; Leu 33?Tyr, Val, Ile, Thr, Phe; Glu 34?Val, Arg, Ala; Leu 56?Asn; Ile 57?Gln; Ser 58?Ile, Val; Asp 80?Tyr; Lys 83?Ala; Glu 104?Asp; Leu 105?Thr; His 106?Trp and Lys 108?Gly. Mutein can also additionally contain the following substitutions: Cys 61?Ser; Cys 101?Ser; Cys 153?Ser; Arg 111?Pro; Lys 114?Trp; Thr 37?Ser; Met 39?Ile, Leu; Asn 48?Ser; Lys 52?Thr, Met; Met 55?Leu; Lys 65?Arg, Leu; Ala 79?Leu, Ser; Ala 86?Thr; Ile 89?Ser, Gln, Thr, His; Thr 40?Cys; Glu 73?Cys; Arg 90?Cys; Asp 95?Cys; Lys 121?Cys; Asn 123?Cys and Glu 131?Cys.EFFECT: invention makes it possible to efficiently treat pathological disorders, which involve pathway HGF/c-Met, as well as to perform identification of human c-Met in sample.40 cl, 16 dwg, 9 tbl, 25 ex |
