Molecular Docking and ADME Analysis of L-Phe -L-Tyr Dipeptide

Abstract

Hypertension is a serious risk factor for various diseases. Therefore, lowering and preventing high blood pressure is a significant issue. Blockage of the renin-angiotensin-aldosterone system (RAAS), which controls blood pressure, is important to reduce blood pressure and consequently reduce symptoms of heart failure. This blockage can be carried out by angiotensin-converting enzyme (ACE) and angiotensin II receptor blockers (ARBs). The phenylalanyltyrosine (H-Phe-Tyr-OH, Phe-Tyr, L-Phe-L-Tyr, L-phenylalanyl-L-tyrosine) dipeptide examined in this study is an important structure that shows blood pressure lowering properties. For this reason, the potential of the peptide to be an ACE inhibitor or ARB was investigated. The molecular activity of the Phe-Tyr dipeptide was compared with antihypertensive drugs using theoretical calculations. Molecular docking method, one of these theoretical methods, has a considerable process in illuminating biochemical processes by investigating the interactions of drugs (ligands) with targeted receptors. In this theoretical study, molecular docking analyses of H-Phe-Tyr-OH dipeptide with ACE and Angiotensin II type 1 receptor (AT1R) were implemented. The interaction types and interaction regions of the peptide were also determined in comparison with drug molecules (Captopril, Enalapril, Telmisartan and Eprosartan) that are ACE inhibitors and ARBs. Lastly, ADME (absorption, distribution, metabolism, and excretion) analysis of the H-Phe-Tyr-OH dipeptide was also performed to estimate its drug potential. In this study, the pharmacokinetic properties of Phe-Tyr dipeptide and its mechanism of action with ACE and AT1R were investigated for the first time by molecular docking and ADME calculations.