Solution structure of casokefamide.

Casokefamide (Tyr-D-Ala-Phe-D-Ala-Tyr-NH2) is a synthetic peptide derived from the beta-casomorphin sequence, designed to increase the resistance to gastric proteases. Casokefamide binds to both mu and delta-opioid receptors, while beta-casomorphins and its fragments are typical mu-opioid receptor agonists. Furthermore, casokefamide can affect gastric acid and pancreatic exocrine secretions and also gastrointestinal motility. We have undertaken a conformational study on this peptide based on NMR measurements in a DMSOd6/H2O cryomixture at 265 K and energy calculations. The predominant conformation is characterised by the absence of regular structures and intramolecular hydrogen bonds. The conformation of the message domain is reminiscent of the shape of several peptidic and non peptidic opiates, with the D-Ala2CH3 group sandwiched between Tyr1 and Phe3 aromatic rings.