Stabilized fibronectin domain compositions, methods and uses

摘要

A protein scaffold based on a consensus sequence of fibronectin type III (FN3) proteins, such as the tenth FN3 repeat from human fibronectin (human Tenascin), including isolated nucleic acids that encode a protein scaffold, vectors, host cells, and methods of making and using thereof, exhibit enhanced thermal and chemical stability while presenting six modifiable loop domains which can be engineered to form a binding partner capable of binding to a target for applications in diagnostic and/or therapeutic compositions, methods and devices.

主权项

1. A protein scaffold comprising loop domains topologically similar to loop domains of a fibronectin type III (FN3) domain, the protein scaffold having an amino acid sequence based on the consensus amino acid sequence of SEQ ID NO: 16, wherein one or more specific residues of SEQ ID NO: 16 are replaced to enhance melting temperature (Tm) and chemical stability of the protein scaffold as compared to the Tm and chemical stability of a protein scaffold having the amino acid sequence of SEQ ID NO: 16, and the replacements of SEQ ID NO: 16 are selected from the group consisting of N46V, E14P, L17A, E86I, a combination of N46V and E86I, a combination of N46V and E86I, and a combination of L17A, N46V and E86I.