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Blood pressure and fluid balance are regulated hormonally by renin-angiotensin system (RAS). Influence on this system could be achieved by different compounds that act as angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers and renin inhibitors. The purpose of the present study is to predict the structures of the potent ACE inhibitors on the base of His-Leu peptide structural element of angiotensine I using computational methods. Different modifications were made in the structure of this dipeptide and the energy of binding with the enzyme were calculated. The docking results were analyzed and it was found that along with the important amino acid residue of the receptor molecule Arg167, the Tyr residues (35, 87, 88 and 92) as well as Cys180 are extremely important for the strong binding to the receptor and, accordingly, the manifestation of antagonistic action by the analogues. To block the receptor, the ligand molecule must have an intact terminal carboxyl group and an imidazole nucleus to participate in appropriate interactions. The inclusion of functional groups in the side chains of the amino acid residues of the dipeptide create an additional site for binding to the receptor. With the help of docking, the ligand molecule can be optimized, and this process is fast, saving the synthesis of many compounds and their biological testing. And finally, the most potent analogues will be synthesized and biologically tested. [ABSTRACT FROM AUTHOR]

The bioactive peptides are specific protein fragments which have a positive effect on the body functions and conditions. These peptides have a hormone- or a drug like activity and play an important role. The antihypertensive peptides are a significant group of these peptides, which are used as angiotensin-converting enzymes inhibitors, because they are associated with the high blood pressure decrease and play an important role in cardiovascular diseases. Angiotensin-I Converting Enzyme (ACE) is one of the major components of the so-called Renin-Angiotensin System (RAS). Renin is responsible for the release of Angiotensin I (AI) in blood because of its catalytic action on angiotensinogen. The role of ACE connected with the inhibition of ACE enzymatic activity against AI is considered one of the major challenges in case of a hypertensive disease and a congestive heart failure. The present investigation is focused on the synthesis of His-Leu and Val-Trp peptide analogues using well know procedures. The intermediates and the dipeptide analogues are characterized by TLC and spectral methods. The computer modeling and the docking studies are performed to determine the structure-activity relationship and to synthesize new potential ACE inhibitors. [ABSTRACT FROM AUTHOR]

Bioactive peptides are protein fragments that have a positive impact on body functions and may ultimately influence health. Angiotensin-converting enzyme plays an important role in the control of arterial blood pressure. The main action of Angiotensin II is to maintain blood pressure and fluid balance in the body. It is obtained from the precursor under catalytic action of angiotensin-converting enzyme (ACE). In order to control (inhibit) the action of the ACE different inhibitors were proposed and some of them are already in use in the clinic. In the present investigation we design and docking studies of fife new potential ACE inhibitors. Three of the proposed analogues have a potential to be ACE inhibitors, as they bind to the enzyme stronger than His-Leu. The studied peptides may form as a basis for the design of new compounds and will be synthesized and biologically tested. [ABSTRACT FROM AUTHOR]