Fibroblast growth factor 1 protein fragments and methods of use

摘要

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 FGF19 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 the present invention.

主权项

1. A method of treating a mammal having diabetes, comprising:
administering an FGF1 peptide comprising amino acids 1-155 of SEQ ID NO: 1 with a K127D, K128Q and K133V substitution (FGF1ΔHBS) in an amount effective to lower blood glucose levels in the mammal, thereby treating the mammal.