Binding polypeptides

A fibronectin type III (Fn3) monobody polypeptide comprising at least two Fn3 β-strand domain sequences with a ioop region linked between each Fn3 β-strand domain sequence, wherein at least one monobody loop region sequence varies as compared to the wild-type (SEQ ID NO:110, FIG. 2) loop region sequence by deletion of two to twelve amino acids in the loop region sequence, insertion of at least two to 25 amino acids, or replacement of at least two amino acids in the loop region sequence, and wherein the monobody polypeptide is capable of binding to a target molecule with a dissociation constant of less than 10−6 moles/liter.