Insulin and IGF-1 receptor agonists and antagonists

Abstract

Peptide sequences capable of binding to insulin and/or insulin-like growth factor receptors with either agonist or antagonist activity and identified from various peptide libraries are disclosed. This invention also identifies at least two different binding sites, which are present on insulin and insulin-like growth factor receptors, and which selectively bind the peptides of this invention. As agonists, the peptides of this invention may be useful for development as therapeutics to supplement or replace endogenous peptide hormones. The antagonist peptides may also be developed as therapeutics.

1 . A method of modulating insulin-like growth factor receptor activity in insulin-like growth factor-responsive mammalian cells comprising: contacting the cells with an amino acid sequence in an amount sufficient to modulate the activity of insulin-like growth factor receptor, wherein i) the amino acid sequence comprises a Formula 1 sequence, X 1 X 2 X 3 X 4 X 5,  such that X 1,  X 2,  and X 5  are selected from the group consisting of phenylalanine and tyrosine, X 3  is selected from the group consisting of aspartic acid, glutamic acid, glycine and serine, and X 4  is selected from group consisting of tryptophan, tyrosine and phenylalanine; and ii) with the proviso that the amino acid sequence is not insulin, insulin-like growth factor, an anti-insulin receptor antibody, an anti-insulin-like growth factor receptor antibody, or fragments thereof.