Design of a novel small peptide targeted against a tumor-specific receptor

EGFRvIII is the most common deletion variant of the epidermal growth factor receptor and is found in cancers of the brain, breast, ovary, and lung. Th e complete absence of the receptor in healthy tissues makes it an ideal tum or marker. We sought to design a peptide ligand against EGFRvIII for develo pment as a diagnostic imaging agent, We used the concept of hydropathic com plementarity to search for sequences whose amino acid sidechains display a reciprocal pattern of hydropathicity to those of the deletion junction of E GFRvIII. The resulting peptide (PEPHC1) was synthesized and tested for bind ing to EGFRvIII and EGFR. In in vitro assays, PEPHC1 bound the recombinant EGFRvIII extracellular domain or full-length EGFRvIII solubilized from cell membranes in preference to native EGFR. These results demonstrate the util ity of hydropathic complementarity as a basis for the design of highly spec ific ligands that may prove useful as tumor-targeting agents, (C) 2000 Acad emic Press.