Abstract: This invention is directed to the discovery of improved methods of preparing cyclic peptides, cyclic peptide esters, cyclic peptide amidines, and libraries of these compounds. The invention also includes uses of these compounds and libraries for screens as drugs and binders of biologics.

Abstract: A method of isolating and identifying peptide substrates for a protein kinase is disclosed. The method involves a combination of size exclusion and gallium-based metal affinity chromatography. The method includes the steps of incubating a protein kinase with a peptide library in the presence of kinase reaction components, the library comprising library members; separating library members from the kinase reaction components using size exclusion chromatography to give a pool of phosphopeptides and unphosphorylated peptides; contacting the pool with immobilized gallium ions to form chelated phosphopeptides; eluting chelated phosphopeptides away from the gallium ions to give eluted phosphopeptides; sequencing the eluted phosphopeptides, whereby a preferred amino acid sequence of a preferred peptide substrate for a protein kinase is elucidated.