Abstract: Modified insulinotropic peptides are disclosed. The modified insulinotropic peptides are capable of forming a peptidase stabilized insulinotropic peptide. The modified insulinotropic peptides are capable of forming covalent bonds with one or more blood components to form a conjugate. The conjugates may be formed in vivo or ex vivo. The modified peptides are administered to treat humans with diabetes and other related diseases.

Abstract: A method for protecting a peptide from peptidase activity in vivo, the peptide being composed of between 2 and 50 amino acids and having a C-terminus and an N-terminus and a C-terminus amino acid and an N-terminus amino acid is described. In the first step of the method, the peptide is modified by attaching a reactive group to the C-terminus amino acid, to the N-terminus amino acid, or to an amino acid located between the N-terminus and the C-terminus, such that the modified peptide is capable of forming a covalent bond in vivo with a reactive functionality on a blood component. In the next step, a covalent bond is formed between the reactive group and a reactive functionality on a blood component to form a peptide-blood component conjugate, thereby protecting said peptide from peptidase activity. The final step of the method involves the analyzing of the stability of the peptide-blood component conjugate to assess the protection of the peptide from peptidase activity.

Abstract: Methods and compositions are provided for identifying compounds having affinity or complementarity to a target molecule. Compounds according to the invention may be described by the formula E-Ca—R—Cb-A, wherein E is a therapeutic or diagnostic agent, R is a reactive group, Ca and Cb are connector groups between E and R and between R and A, respectively, and A is a group having an affinity for human serum albumin, wherein affinity group A comprises a sequence of amino acid residues —O1—O2—X1—X2—B in which the amino acid residues are independently selected from the group of all twenty naturally occurring amino acids. Compounds according to the invention may be used for labeling the target molecule, particularly where the target molecule is naturally found in a complex mixture, such as a physiological fluid, like blood. By affinity labeling in vivo, the lifetime of physiologically active entities can be greatly enhanced by becoming bound to long-lived blood components.