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Testing hormone mimic function against biological protein targets implied in human health

Faculty Mentor: Danielle Guarracino

Students: Jessica Gruskos & Ari Goldwaser

Vasopressin and Oxytocin are two naturally occurring hormones with biological importance. Vasopressin helps regulate water levels in the body, and lack of vasopressin is associated with Neurogenic Diabetes Insipidus (DI). Oxytocin has many biologically important functions such as initiating uterine contraction, cell signaling, and regulating certain behaviors (autism, anxiety, etc). Cyclized peptides that imitate these hormones have been designed. Our peptides incorporate small, but significant, changes thought to improve stability in comparison with the natural hormones. Vasopressin “mimics” could rescues Vasopressin function in DI while Oxytocin “mimics” could be applicable to a range of disorders.

This summer we continued the research that the Guarracino research group had been previously conducting during the past semesters.  One Oxytocin mimic and two Vasopressin mimics were synthesized, purified, and their stabilities were tested against three different peptide-degrading factors that emulate the cellular condition: pepsin, pronase, and α-chymotrypsin. All the hormone mimics proved to be more stable than the natural hormones and a linear control peptide. Additionally, during MUSE a method was developed to test the binding affinity of the hormone mimics to their appropriate cell receptor. The V2 vasopressin receptor is fundamental in bodily maintenance of water homeostasis. The binding affinities of natural Vasopressin and Vasopressin mimic 1 for the V2 cell receptor were tested. We showed that Vasopressin mimic 1 binds to the V2 receptor and competes with natural Vasopressin for binding. While Vasopressin mimic 1 has a 1-fold weaker binding affinity compared to natural Vasopressin, this supports the potential for these mimics as first generation pharmaceutical models.  Further optimization of the Vasopressin and Oxytocin mimic design and determination of other mimic binding affinities will be tested in the future.

 

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