CD, UV, and In Silico Insights on the Effect of 1,3-Bis(1′-uracilyl)-2-propanone on Serum Albumin Structure

Abstract

1,3-diaryl-2-propanone derivatives are synthetic compounds used as building blocks for the realization not only of antimicrobial drugs but also of new nanomaterials thanks to their ability to self-assemble in solution and interact with nucleopeptides. However, their ability to interact with proteins is a scarcely investigated theme considering the therapeutic importance that 1,3-diaryl-2-propanones could have in the modulation of protein-driven processes. Within this scope, we investigated the protein binding ability of 1,3-bis(1′-uracilyl)-2-propanone, which was previously synthesized in our laboratory utilizing a Dakin–West reaction and herein indicated as U2O, using bovine serum albumin (BSA) as the model protein. Through circular dichroism (CD) and UV spectroscopy, we demonstrated that the compound, but not the similar thymine derivative T2O, was able to alter the secondary structure of the serum albumin leading to significant consequences in terms of BSA structure with respect to the unbound protein (Δβ-turn + Δβ-sheet = +23.6%, Δα = −16.7%) as revealed in our CD binding studies. Moreover, molecular docking studies suggested that U2O is preferentially housed in the domain IIIB of the protein, and its affinity for the albumin is higher than that of the reference ligand HA 14−1 (HDOCK score (top 1–3 poses): −157.11 ± 1.38 (U2O); −129.80 ± 6.92 (HA 14−1); binding energy: −7.6 kcal/mol (U2O); −5.9 kcal/mol (HA 14−1)) and T2O (HDOCK score (top 1–3 poses): −149.93 ± 2.35; binding energy: −7.0 kcal/mol). Overall, the above findings suggest the ability of 1,3-bis(1′-uracilyl)-2-propanone to bind serum albumins and the observed reduction of the α-helix structure with the concomitant increase in the β-structure are consistent with a partial protein destabilization due to the interaction with U2O.

New N4-Donor Ligands as Supramolecular Guests for DNA and RNA: Synthesis, Structural Characterization, In Silico, Spectrophotometric and Antimicrobial Studies

“…We performed molecular docking simulations [ 60 , 61 , 62 , 63 ] with the HDOCK server ( , accessed on 20 September 2022) [ 64 , 65 ], suitable for both macromolecule-to-macromolecule [ 64 ] and macromolecules-to-small molecule [ 66 ] rigid dockings, using default parameters. The PDB entries 1BNA [ 44 ], relative to the DNA dodecamer d(CpGpCpGpApApTpTpCpGpCpG), and 1U2A, relative to the stem-loop IIa from yeast U2 small nuclear RNA [ 45 ], were used as models of DNA and RNA, respectively, for our blind dockings.…”

Interaction of Laurusides 1 and 2 with the 3C-like Protease (Mpro) from Wild-Type and Omicron Variant of SARS-CoV-2: A Molecular Dynamics Study

“…These structures were then used as templates to create whole models of the systems, filling the structural gaps, by homology modelling with MODELLER 9.22 program [ 50 ]. The three-dimensional structures of the two laurusides compounds were obtained by MOLVIEW ( , accessed on 9 February 2023) in analogy to other literature examples [ 51 , 52 ], saved as .pdb files, and manually complexed into the M pro variants using the binding pose of Nirmatrelvir in PDB 7TLL as a guide [ 47 ]. In particular, the coordinates of the Nirmatrelvir were used for the binding pocket definitions in order to insert both the laurusides, upon superimposition of the two variant models on the 7TLL X-ray structure of Nirmatrelvir in complex with Omicron M pro .…”

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

“…The molecular docking investigations described in this study made use of the HDOCK software [29,30]. HDOCK is a widely utilized computational tool for conducting docking simulations involving macromolecules, including proteins [31,32]. Through the utilization of ITScore-PP, an iterative knowledge-based scoring function, HDOCK ranks the top poses generated during docking runs, typically providing the top 1-10 poses.…”