Abstract: The present invention relates to a polypeptide comprising 7 ?-strands A, B, C, D, E, F, and G sequentially connected together by connecting chains of amino acids, and a first ?-helix sequentially located on the EF chain between ?-strands E and F, wherein the ?-strands are arranged so as to form a first ?-sheet comprising ?-strands A, B, D, and E, and a second ?-sheet comprising ?-strands C, F and G, said first and second ?-sheets being covalently bonded together so as to form a first Ig domain; wherein the EF chain between ?-strands E and F comprises the sequence X1-X2-X3-X4-K5H6 (SEQ ID NO:98), and X1, X3 and X4 are each independently any amino acid residue, characterized in that X2 is selected from the group consisting of A, G, I, V, L, R, S, T, Q, P, N, M, H, W, and pharmaceutically acceptable salts, stereoisomers, tautomers, solvates, and prodrugs thereof

Abstract: The present invention provides a composition of the formula: [FGF21-1st Linker]-[Ab]-[2nd-Linker-Ex4]; wherein FGF21 is an FGF21 homologue; and Ex4 is an Exendin4 homologue; and Ab is an aldolase catalytic antibody or antigen binding portion thereof; and the 1st linker is covalently attached to the side chain of a protein-linking residue in FGF21 and to a combining site of the antibody, and the 2nd linker is covalently attached to the side chain of a peptide-linking residue in Ex4 and to a combining site of the antibody, and wherein the first and second linker are the same or different. Various uses of the compounds are provided, including methods to prevent or treat diabetes or diabetes-related conditions.