Novel, potent calmodulin antagonists derived from an all-dhexapeptide combinatorial library that inhibitin vivocell proliferation: activity and structural characterization

: Calmodulin is known to bind to various amphipathic helical peptide sequences, and the calmodulin–peptide binding surface has been shown to be remarkably tolerant sterically. d-Amino acid peptides, therefore, represent potential non-hydrolysable intracellular antagonists of calmodulin. In the present study, synthetic combinatorial libraries have been used to develop novel d-amino acid hexapeptide antagonists to calmodulin-regulated phosphodiesterase activity. Five hexapeptides were identified from a library containing over 52 million sequences. These peptides inhibited cell proliferation both in cell culture using normal rat kidney cells and by injection via the femoral vein following part…