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Artigo
Structural parameters of the interaction between ciprofloxacin and human topoisomerase-II β enzyme: toward new 19F NMR chemical shift probes
(2022-12-07) Sales, Thais Aparecida; Gonçalves, Mateus Aquino; Ramalho Teodorico Castro
New tools for cancer diagnosis are being studied day by day, since early diagnosis can be crucial for a successful treatment. In this context, the use of NMR probes constitutes an efficient way of diagnosis. In this work, we investigated the use of ciprofloxacin to indirectly label the overexpression of topoisomerase-II enzymes by changes in 19F NMR chemical shifts of ciprofloxacin. Increased topoisomerase-II expression has been associated with cancer occurrence, mainly with aggressive forms of breast cancer, thus constituting a promising molecular targetfor new tumor cell identifiers. Using DFT calculations, a spectroscopy analysis of ciprofloxacin in different chemical environments, evaluating the solvent and enzymatic effects was performed. Our results point that the ciprofloxacin forms a stable complex with the enzyme, and the main intermolecular interactions between ciprofloxacin and human topoisomerase-IIβ are hydrogen bonds, following by pi-pi stacking and electrostatic interactions. Also, a shift of 6.04 ppm occurs in the 19F NMR signal when ciprofloxacin is interacting with the human topoisomerase-IIβ enzyme, and that this parameter may be a possible indirect marker to indicate the overexpression of these enzymes in the body.
Artigo
Improved protocol for the selection of structures from molecular dynamics of organic systems in solution: the value of investigating different wavelet families
(2022-09-14) Gonçalves, Mateus A.; Gonçalves, Arlan S.; Franca, Tanos C. C.; Santana, Mozarte S.; Cunha, Elaine F. F. da; Ramalho, Teodorico C.
Wavelets are mathematical tools used to decompose and represent another function described in the time domain, allowing the study of each component of the original function with a scale-compatible resolution. Thus, these transforms have been used to select conformations from molecular dynamics (MD) trajectories in systems of fundamental and technological interest. Recently, our research group has used wavelets to develop and validate a method, meant to select structures from MD trajectories, which we named OWSCA (optimal wavelet signal compression algorithm). Here, we moved forward on this project by demonstrating the efficacy of this method on the study of three different systems (non-flexible organic, flexible organic, and protein). For each system, 93 wavelets were investigated to verify which is the best one for a given organic system. The results show that the best wavelets were different for each system and, also, very close to the experimental values, with the wavelets db1, rbio 3.1, and bior1.1 being selected for the non-flexible, flexible organic, and protein systems, respectively. This reinforces our OWSCA as a very efficient and promising method for the selection of structures from MD trajectories of different classes of compounds. Our findings also point out that additional studies considering wavelet families are needed for defining the best wavelet for representing each system under study.
Artigo
Exploring EPR parameters of 187 Re complexes for designing newMRI probes: from the gas phase to solution and a modelprotein environment
(2022-11-10) Andolpho, Gustavo A.; Cunha, Elaine F. F. da; Ramalho, Teodorico C.
Breast cancer is one of the major types of cancer around the world, and early diagnosis is essential for successful treatment. Newcontrast agents (CAs), with reduced toxicology, are needed to improve diagnosis. One of the most promising Magnetic ResonanceImaging (MRI) CA is based on rhenium conjugated with a benzothiazole derivate (ReABT). In this sense, DFT has been used toevaluate the best methodology for calculating the hyperfne coupling constant (Aiso ) of ReABT. Ten, a thermodynamic analysiswas performed to confrm the stability of the complex. Furthermore, a docking study of ReABT at the enzyme PI3K active site andAiso calculations of ReABT in the enzyme environment were carried out. Te best methodology for the Aiso calculation of ReABTwas using the M06L functional, SARC-ZORA-TZVP (for Re) and TZVP (for all other atoms) basis set, relativistic Hamiltonian,and the CPCM solvation model with water as the solvent which confrm that the relativistic efects are important for calculatingthe Aiso values. In addition, thermodynamic analysis indicates that ReABT presents a higher stability and a lower toxicity than Gd-based CAs. Te docking studies point out that ReABT interacts with amino acids residues of alanine, aspartate, and lysine from thePI3K active site. Considering the enzyme environment, Aiso values decrease signifcantly. Tese fndings indicate that the CAcandidate ReABT could be a good candidate for a new contrast agent.
Artigo
Exploring 129Xe NMR parameters for structural investigation of biomolecules: relativistic, solvent, and thermal effects
(2022-11-01) Gonçalves, Mateus A.; Andolpho, Gustavo A.; Cunha, Elaine F. F. da; Ramalho, Teodorico C.
In recent years, the study of new probes has aroused great interest in the scientific community around the world. Therefore, in the present work, we present a potential candidate for a new spectroscopic probe, the Xe(CO)3(NNO) conjugated to 2-(4′-aminophenyl) benzothiazole complex, XeABT. For this proposal, chemical shift calculations at the DFT level were performed; thus, a factorial design was carried out in order to choose the best computational method. The best combination was the base function ZORA-def2-TZVP, with the functional PBE0 and considering the relativistic effects with the ZORA implementation. Our findings reveal that the 129Xe chemical shifts are affected by thermal and solvent effects, and considering an enzymatic environment, a significant decrease in δ(129Xe) values is observed, suggesting with the XeABT complex it may be a promising spectroscopic probe.
Artigo
A taxatividade do rol de procedimentos da Agência de Saúde Suplementar e a negativa de tratamento às pessoas com transtorno do espectro autista
(2022-11) Divino, Sthéfano Bruno Santos; Antunes, Beatriz Gaia Barreto