Novel octapeptide containing the RGD sequence as a potential anti-SARS-CoV-2 agent: design, synthesis, and...

Area of Science:

• Biochemistry
• Medicinal Chemistry
• Molecular Biology

Background:

• Peptide-based inhibitors targeting cell receptors are a promising strategy for developing antiviral agents.
• Integrins are key cell receptors involved in viral entry and pathogenesis.

Purpose of the Study:

• To design and synthesize a novel octapeptide containing the RGD sequence for potential interaction with integrins.
• To evaluate the conformational, physicochemical, and binding properties of the designed peptide.

Main Methods:

• Rational design of an octapeptide with an RGD sequence and malonic moiety.
• Density Functional Theory (DFT-PBEh-3c) calculations for property evaluation.
• Molecular docking studies to predict interactions with integrin α5β1.
• Fmoc-based solid-phase peptide synthesis (SPPS) for peptide production.
• Characterization using NMR, IR, MS, and RP-HPLC.

Main Results:

• The designed octapeptide exhibited favorable predicted interactions with integrin α5β1, including coordination with the active site Mg²⁺ ion.
• The peptide was successfully synthesized and characterized, confirming its structure and purity.
• Computational analysis provided insights into the peptide's conformational and physicochemical properties.

Conclusions:

• The novel RGD-containing octapeptide demonstrates potential as an integrin-targeting antiviral agent.
• The malonic functionalization may enhance binding capabilities and bioactivity.
• This study provides a foundation for further development of peptide-based antivirals targeting integrins.