Vasopressin and Oxytocin are peptide hormones naturally produced in the pituitary and hypothalamus glands, respectively. Both are cyclic peptides similar in sequence and held in a ring via a disulfide bond. The disease Neurogenic Diabetes Insipidus, characterized by a deleterious electrolyte imbalance in those afflicted, is attributed to a deficiency in Vasopressin. As a result, current research is dedicated to creating compounds with the capability of rescuing Vasopressin's function. The mimics described herein maintain the overall 3D structure of the parent hormones, but feature a head-to-tail cyclization and smaller overall ring sizes. Alterations were expected to increase mimic stability in the presence of protease enzymes, a hallmark of their overall bioavailability as drugs. Each mimic was treated with a panel of proteases at body temperature over progressive time. The resultant percent degradation was calculated for each compound. The results clearly verified that mimic peptides display increased proteolytic stability as compared with controls. This testifies to their candidacy as first generation pharmaceuticals. Current studies are assaying the mimics' ability to compete with hormones for binding their cell receptors. In the future, the compounds will be evaluated in a mammalian cell reporter assay, to see if the mimics elicit the same cellular response as the hormones. 

Development of hormone mimics with increased protease stability and implications in human health

243rd National Meeting (2012)

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