Analogs of pancreatic polypeptide and peptide YY with a locked PP-fold structure are biologically active

► PP, PYY and NPY can adopt a highly organized tertiary structure, the PP-fold. ► PP-fold structure has long been assumed to be the active conformation of this family of peptides. ► Cyclic analogs of PP and PYY, locked in the PP-fold were produced. ► Analogs had similar receptor affinity and biological activity to native peptides. ► Results suggest the PP-fold may well constitute the active form of the peptides.