Angiotensin converting enzyme inhibitors (ACEIs) are often considered first-line therapy for hypertension but not all ACEIs are effective enough to be therapeutically viable. Some natural ACEIs such as alanine-valine-phenylalanine (AVF) are considered inhibitors but have to be present at very high concentrations in order to have an effect. Specifically, AVF has a half maximal inhibitory concentration (IC<sub>50</sub>) value of 2123μM. This high value suggests that AVF does not inhibit ACE well enough to be therapeutically viable. It is important to have options for therapeutically viable ACE inhibitors because of their role in combatting hypertension. This study is dedicated to investigating the effect of specific structural changes on the IC<sub>50</sub> value of alanine-valine-phenylalanine. Structural modifications will be made to valine and phenylalanine, with four different groups being added to each amino acid and a total of eight different tri-peptides synthesized. NMR and HPLC will be used to assess the structure and chirality, respectively, of the modified peptides. Successfully formed tri-peptides will be analyzed using an in vitro assay to determine if they have retained or improved their ACEI properties. In this analysis, a known ACE inhibitory drug will be used and dose response curve produced to confirm effectiveness of the model. Then, AVF will be run through this assay to find the concentration needed to produce a statistically significant effect. Once this control data is collected, the eight modified compounds can be analyzed in the same way. Results from this study will be presented.

Structural modification of a natural angiotensin converting enzyme inhibitor and the effect on activity

2019 Spring National Meeting

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