Angiotensin(1-7)-Stearic Acid Conjugate: Synthesis and Characterization

Year 2022, Volume: 9 Issue: 2, 331 - 338, 31.05.2022

Tayfun Acar , Burcu Uçar

https://doi.org/10.18596/jotcsa.1032642

Cited By: 1

Abstract

The novel coronavirus, SARS-CoV-2, broken out as the COVID-19 epidemic, is transported into the cytoplasm by angiotensin-converting enzyme-2 (ACE2), a key protein of the renin-angiotensin-system (RAS). ACE2 is a protective protein that reduces angiotensin (Ang) II, the bioactive component of RAS, by converting it to its potent antagonist, Ang-(1-7) peptide, in order to provide a pathophysiological response to stimuli. Although ACE-2 is upregulated especially in pulmonary endothelial cells and alveolar epithelial cells, downregulation of ACE-2 in the lung owing to loss of key regulatory factors explains the enzyme-dependent lethality of SARS-CoV-2. The N-terminal domain (NTD) of S1, one of the protein subunits of coronaviruses, is known to recognize acetylated sialic acids on glycosylated cell surface receptors. In this study, the stearic acid-peptide conjugate mimicking the sialic acid structure was synthesized, which will be able to balance uncontrolled inflammatory response and excessive cytokine production, and depending on these to suppress pneumonia and acute respiratory distress syndrome (ARDS), against SARS-CoV-2. It was expected that fatty acid acylation would greatly enhance cellular internalization and cytosolic distribution of the peptide through the cell membrane. Thus, we synthesized fatty acyl derivative of the N-Ac-Gly4-Ang (1-7) peptide. The peptide was synthesized using Fmoc/tBu solid-phase peptide chemistry and characterized by FT-IR, Zetasizer, and LC-ESI-MS. This study provided more detailed insights into understanding and meeting the basic structural requirements for optimal cellular delivery and formulation of the stearyl Ang (1-7)-peptide conjugate.

Keywords

COVID-19, Solid phase peptide synthesis, Angiotensin (1-7), Conjugation

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