Structure-function studies of peptides for cell adhesion inhibition: identification of key residues by alanine mutation and peptide-truncation approach.

Blockage of the interaction of CD2 with its ligand CD58 is expected to bring out potential therapeutic value for autoimmune diseases and organ transplantation. Three series of peptides (cVL, cIL and cAQ series) were designed from ratCD2 and humanCD2 to modulate CD2-CD58 interaction. To determine the specific segments in parent peptides responsible for inhibitory activity as lead sequence, we generated shorter fragments of the parent peptides and evaluated their biological activity with cell adhesion assay. The structure-activity relationship studies indicated that small cyclic peptides derived from CD2 ligand binding epitopes could mimic native beta-turn structure, and thus modulate CD2-CD58 interaction.