Abstract: Therapeutic compositions for treatment of protein serine/threonine phosphatase-related diseases are obtained by engineering amino acid sequences that disrupt interaction between the protein serine/threonine phosphatase and a protein inhibitor and are provided herein. Calcineurin and PPI are examples of protein serine/threonine phosphatases. RCAN1 is an inhibitor of calcineurin and is overexpressed in patients with serious diseases, such as Down syndrome and Alzheimer's disease. Molecules that bind RCAN1 at regions that interact with calcineurin selectively modulate functions of calcineurin to treat these diseases. Methods of treating a subject for a protein serine/threonine phosphatase-related disease by administering a molecule having an amino acid sequence selected from the group of SEQ ID NOs: 1-19 are further provided.

Abstract: Cancer, obesity, and diabetes are examples of PTP1B-related diseases. The invention herein provides embodiments of therapeutic methods and compositions for treating PTP1B related diseases by engineering peptides that bind to the functional spine of PTP1B to alter the conformation of the protein and inhibit a function of PTP1B. Molecules bind to amino acid residues of the functional spine of PTP1B, regulate the catalytic cycle, and treat PTP1B-related diseases. For example, molecules bind to at least one of Tyr152, Tyr153, His175, Thr178, Pro185, Phe191, Leu192, Asn193, Cys215, Gly218, Phe280, Val287, Trp291, Lys292, Leu294, Ser295, and Glu297 to reduce at least one symptom of a PTP1B related disease.

Abstract: Therapeutic compositions for treatment of protein serine/threonine phosphatase-related diseases are obtained by engineering amino acid sequences that disrupt interaction between the protein serine/threonine phosphatase and a protein inhibitor and are provided herein. Calcineurin and PPI are examples of protein serine/threonine phosphatases. RCAN1 is an inhibitor of calcineurin and is overexpressed in patients with serious diseases, such as Down syndrome and Alzheimer's disease. Molecules that bind RCAN1 at regions that interact with calcineurin selectively modulate functions of calcineurin to treat these diseases. Methods of treating a subject for a protein serine/threonine phosphatase-related disease by administering a molecule having an amino acid sequence selected from the group of SEQ ID NOs: 1-19 are further provided.