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BSA Binding and Aggregate Formation of a Synthetic Amino Acid with Potential for Promoting Fibroblast Proliferation: An In Silico, CD Spectroscopic, DLS, and Cellular Study
Simonyan, H.; Palumbo, R.; Petrosyan, S.; Mkrtchyan, A.; Galstyan, A.; Saghyan, A.; Scognamiglio, P.L.; Vicidomini, C.; Fik-Jaskólka, M.; Roviello, G.N. BSA Binding and Aggregate Formation of a Synthetic Amino Acid with Potential for Promoting Fibroblast Proliferation: An In Silico, CD Spectroscopic, DLS, and Cellular Study. Biomolecules2024, 14, 579.
Simonyan, H.; Palumbo, R.; Petrosyan, S.; Mkrtchyan, A.; Galstyan, A.; Saghyan, A.; Scognamiglio, P.L.; Vicidomini, C.; Fik-Jaskólka, M.; Roviello, G.N. BSA Binding and Aggregate Formation of a Synthetic Amino Acid with Potential for Promoting Fibroblast Proliferation: An In Silico, CD Spectroscopic, DLS, and Cellular Study. Biomolecules 2024, 14, 579.
Simonyan, H.; Palumbo, R.; Petrosyan, S.; Mkrtchyan, A.; Galstyan, A.; Saghyan, A.; Scognamiglio, P.L.; Vicidomini, C.; Fik-Jaskólka, M.; Roviello, G.N. BSA Binding and Aggregate Formation of a Synthetic Amino Acid with Potential for Promoting Fibroblast Proliferation: An In Silico, CD Spectroscopic, DLS, and Cellular Study. Biomolecules2024, 14, 579.
Simonyan, H.; Palumbo, R.; Petrosyan, S.; Mkrtchyan, A.; Galstyan, A.; Saghyan, A.; Scognamiglio, P.L.; Vicidomini, C.; Fik-Jaskólka, M.; Roviello, G.N. BSA Binding and Aggregate Formation of a Synthetic Amino Acid with Potential for Promoting Fibroblast Proliferation: An In Silico, CD Spectroscopic, DLS, and Cellular Study. Biomolecules 2024, 14, 579.
Abstract
This study presents the chemical synthesis, purification, and characterization of a novel non-natural synthetic amino acid. The compound was synthesized in solution, purified, and characterized using NMR spectroscopy, polarimetry, and melting point determination. Dynamic Light 22 Scattering (DLS) analysis demonstrated its ability to form aggregates with an average size of 391 nm, extending to low micrometric sizes. Furthermore, cellular biological assays revealed its ability to enhance fibroblast cell growth, highlighting its potential for tissue regenerative applications. Circular dichroism (CD) spectroscopy showed the ability of the synthetic amino acid to bind serum albumins (using bovine serum albumin (BSA) as a model), and CD deconvolution provided insights into the changes in secondary structures of BSA upon interaction with the amino acid ligand. Additionally, molecular docking using HDOCK software elucidated the most likely binding mode of the ligand inside the BSA structure. We also performed in silico oligomerization of the synthetic compound in order to obtain a model of aggregate to investigate computationally. More in detail, in the dimer formation achieved by molecular self-docking, two distinct poses were observed, corresponding to the lowest and comparable energies, with one pose exhibiting a quasi-coplanar arrangement characterized by a close alignment of two aromatic rings from the synthetic amino acids within the dimer, suggesting the presence of π-π stacking interactions. In contrast, the second pose displayed a non-coplanar configuration, with the aromatic rings oriented in a staggered arrangement, indicating distinct modes of interaction. Both poses were further utilized in the self-docking procedure. Notably, iterative molecular docking of amino acid structures resulted in the formation of higher-order aggregates, with a model of a 512-mer aggregate obtained through self-docking procedures. This model of aggregate presented a cavity capable of hosting therapeutic cargoes and biomolecules, rendering it a potential scaffold for cell adhesion and growth in tissue regenerative applications. Overall, our findings highlight the potential of this synthetic amino acid for tissue regenerative therapeutics and provide valuable insights into its molecular interactions and aggregation behavior.
Keywords
in silico; protein binding; self-assembling system; synthetic amino acid; fibroblast growth enhancement; tissue regeneration
Subject
Chemistry and Materials Science, Applied Chemistry
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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