嵌合成纤维细胞生长因子21蛋白及其使用方法

• Format: Patent
• Language: Chinese
• Published: 27.04.2018
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; ENZYMOLOGY; FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIREDCHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERSFROM A RACEMIC MIXTURE; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPIRITS; VINEGAR; WINE

本发明涉及包括偶连于C末端的N末端的嵌合蛋白，其中N末端包括旁分泌成纤维细胞生长因子("FGF")的部分并且C末端包括FGF21分子的C末端部分。旁分泌FGF的所述部分被修饰来相较于不具有所述修饰的部分，减小针对肝素和/或硫酸类肝素的结合亲和力。本发明还涉及包括根据本发明的嵌合蛋白的药物组合物，用于治疗患有糖尿病、肥胖症或代谢综合征的受试者的方法，和筛选具有增强的针对βKIotho-FGF受体复合物的结合亲和力的化合物的方法，所述方法涉及本发明的嵌合蛋白的使用。 The present invention relates to a chimeric protein that includes an N-terminus coupled to a C-terminus, where the N-terminus includes a portion of a paracrine fibroblast growth factor ("FGF") and the C-terminus includes a C-terminal portion of an FGF21 molecule. The portion of the paracrine FGF is modified to decrease binding affinity for heparin and/or heparan sulfate compared to the portion without the modification. The present invention also relates to pharmaceutical compositions including chimeric proteins according to the present invention, methods for treating a subject suffering from diabetes, obesity, or metabolic syndrome, and methods of screening for compounds with enhanced binding affinity for the βKlotho-FGF receptor complex involving the use of chimeric proteins of