Fluorinase reactive substrate analysis

• Grant number: 20/06536-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: July 01, 2020
• End date: February 28, 2022
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Rodrigo Antonio Cormanich
• Grantee: João Paulo Menezes Spadeto
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 18/03910-1 - Physicochemical studies of fluorinated organic compounds: experimental and theoretical approaches, AP.JP

Abstract

The fluorinase enzyme is the only protein known to catalyze the formation of C-F bonds in nature. The enzyme is responsible for the biological formation of the C-F bond in the fluoracetic acid biosynthesis in tropical plants and subtropical. In Brazil these plants are one of the main responsibles for the death of approximately 98.000 cattle per year (US$ 19,600,000.00). In Medicinal Chemistry programs, F is commonly used to replace H, since the C-H bond and C-F bonds have similarities in length and size. However, this substitution has pronounced electronic consequences and can drastically alter the pKa of adjacent functional groups. Due to these changes caused by the addition of a F atom, organofluorinated compounds move billions of dollars every year, in which 20-25% of drugs and 30% of agrochemicals on the market today have F atoms. In the composition of these organic products there is at least one F atom, which makes them more selective and easy to administer compared to their non-fluorinated analogues. These are the factors that make important the research related to the development of organofluorine compounds. Thus, understanding the fluorinase enzyme, such as protein composition, reaction mechanism and forms of interaction, is promising for the development of organofluorinated compounds and, therefore, will be the main objective of this project. These studies will be done by a theoretical research using the techniques of docking and molecular dynamics. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SPADETO, JOAO P. M.; CORMANICH, RODRIGO A.; FRANCA, TANOS C. C.; LAPLANTE, STEVEN R.; GONCALVES, ARLAN S.. Docking and molecular dynamics studies of potential new leads against DBL3x derived from chondroitin sulfate A (CSA): a new approach for the treatment of malaria. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, APR 2021. (18/03910-1, 20/06536-3)

SPADETO, JOAO P. M.; CORMANICH, RODRIGO A.; FRANCA, TANOS C. C.; LAPLANTE, STEVEN R.; GONCALVES, ARLAN S.. Docking and molecular dynamics studies of potential new leads against DBL3x derived from chondroitin sulfate A (CSA): a new approach for the treatment of malaria. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, v. 40, n. 18, p. 10-pg., 2021-04-05. (18/03910-1, 20/06536-3)

MENEZES SPADETO, JOAO PAULO; FREITAS, MATHEUS P.; CORMANICH, RODRIGO A.. Fluorinated dihydropyridines as candidates to block L-type voltage-dependent calcium channels. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, OCT 2021. (20/06536-3, 18/03910-1)

BEZERRA, JULIA N.; SPADETO, JOAO PAULO M.; DARE, JOYCE K.; ALMEIDA, WANDA PEREIRA; FREITAS, MATHEUS P.; CORMANICH, RODRIGO A.. In Silico Interactions of the Components from the Schinus terebinthifolius Extract with Human Tyrosinase. CHEMPLUSCHEM, v. 87, n. 8, p. 12-pg., 2022-08-01. (20/06536-3, 18/03910-1)

STIVANIN, MATEUS L.; GALLO, RAFAEL D. C.; SPADETO, JOAO PAULO M.; CORMANICH, RODRIGO A.; JURBERG, IGOR D.. visible light-mediated three-component strategy based on the ring-opening of cyclic ethers with aryldiazoacetates and nucleophile. ORGANIC CHEMISTRY FRONTIERS, v. 9, n. 5, p. 1321-1326, MAR 1 2022. (20/00144-6, 20/06536-3, 18/03910-1, 19/01235-8)

MENEZES SPADETO, JOAO PAULO; FREITAS, MATHEUS P.; CORMANICH, RODRIGO A.. Fluorinated dihydropyridines as candidates to block L-type voltage-dependent calcium channels. JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, v. 40, n. 24, p. 16-pg., 2022-01-01. (20/06536-3, 18/03910-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SPADETO, João Paulo Menezes. Studies of biological systems using molecular modelling. 2022. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Instituto de Química Campinas, SP.