METHODS FOR MODULATING BILE ACID HOMEOSTASIS AND TREATMENT OF BILE ACID DISORDERS AND DISEASES Russian patent published in 2018 - IPC C12P21/02 C07K14/50 G01N33/92 

FIELD: biotechnology.

SUBSTANCE: invention relates to biotechnology. Method for treating a disorder associated with or associated with the action of bile acids, comprising administering a peptide sequence, is described. While the peptide contains: a) N-terminal region, comprising at least seven amino acid residues, and b) C-terminal region. N-terminal region comprises DSSPL (SEQ ID NO: 121) or DASPH (SEQ ID NO: 122). C-terminal region comprises: (I) the first sequence of the C-terminal region comprising WGDPIRLRHLYTSG (amino acid residues 16–29 of the sequence SEQ ID NO: 99 [FGF19]), where the residue the W residue corresponds to the first amino acid position of the C-terminal region, and (II) a second sequence of the C-terminal region, containing PHGLSSCFLRIRADGVVDCARGQSAHSLLEIKAVALRTVAIKGVHSVRYLCMGADGKMQGLLQYSEEDCAFEEEIRPDGYNVYRSEKHRLPVSLSSAKQRQLYKNRGFLPLSHFLPMLPMVPEEPEDLRGHLESDMFSSPLETDSMDPFGLVTGLEAVRSPSFEK (amino acid residues 30–194 sequence SEQ ID NO: 99 [FGF19]), or a sequence containing from 1 to 5 amino acid substitutions, deletions or insertions. Peptide (I) binds to a receptor for fibroblast growth factor 4 (FGFR4) with an affinity equal to or greater than the binding affinity of FGF19 for FGFR4; (II) activates FGFR4 in a degree or amount equal to or greater than FGF19; (III) has one of the reduced formation of hepatocellular carcinoma (HCC), increased activity in reducing glucose levels, decreased activity in respect of increasing lipid levels, decreased activity in respect of increasing triglycerides, decreased activity in increasing cholesterol, reduced activity in an increase in the level of non-HDL or HDL compared to FGF19 or compared to the sequence of the FGF19 variant, where the WGDPI sequence in amino acid positions 16–20 FGF19 (SEQ ID NO: 99) is replaced by any of GQV, GDI, WGPI, WGDPV, WGDI, GDPI, GPI, WGQPI, WGAPI, AGDPI, WADPI, WGDAI, WGDPA, WDPI, WGDI, WGDP; or FGDPI and/or (IV) has low activity in reducing muscle mass compared to FGF21. Method for modulating bile acid homeostasis is also presented.

EFFECT: methods for modulating bile acid homeostasis and treatment of bile acids disorders and diseases are proposed.

150 cl, 7 dwg, 14 tbl, 12 ex