Enzyme ligand: new models of screening

• Grant number: 13/01710-1
• Support Opportunities: Research Projects - Thematic Grants
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Quezia Bezerra Cass
• Grantee: Quezia Bezerra Cass
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Pesquisadores principais: Carmen Lúcia Cardoso
• Associated researchers: Arthur Henrique Cavalcante de Oliveira ; Dulce Helena Ferreira de Souza ; Emerson Rodrigues de Camargo
• Associated scholarship(s): 16/23794-0 - Stereochemistry of complex natural compounds by vibrational optical activity: acetogenins, BP.PD; 16/14482-5 - Nanofractionation LC-MS/MS and at-line Bioassays for identification of bioactive components in Natural products extracts, BE.PQ; 16/02873-0 - Acetylcholinesterase and beta-secretase 1: a study of co-immobilization conditions for screening of ligands, BP.DR; + associated scholarships 15/25755-0 - Immobilization and characterization of the enzyme trypsin reactor for use in proteomic analysis, BP.IC; 14/11640-3 - LC-MS / 2D methods for screening ligands for evaluating enzyme inhibitory activity and identification of active compounds in crude extracts, BP.PD; 14/21852-8 - Acetylcholinesterase from Atta Sexdens (leaf-cutter ants): development of a system to expression, purification and functional characterization, BP.PD; 14/06907-0 - Immobilization nucleoside diphosphate kinase (NDK) enzyme Leishmania major: the study of conditions for the application in the screening of ligands, BP.DD; 13/02054-0 - Enzyme immobilization: new tools for ligand screening, BP.PD - associated scholarships

Abstract

Several high-throughput assay strategies have been developed for the discovery of protein ligand; among them, frontal (FAC), Zonal (LZC) and nonlinear (NLC) chromatography with immobilized enzymes. The outstanding advantage of bioaffinity chromatography is the easy thermodynamics, kinetics and chemical ligand characterization, in an on-line hyphenated system. This project addresses the development and characterization of enzyme-based stationary phases, and the application of these phases in the development of new screening technologies. The use of ligand fishing and missing peak chromatography and or ligand fishing and dereplication by MS/MS approaches will be explored. A series of enzymes, including the cholinesterases, nucleoside-diphosphate kinase, phosphenolpyruvate carboxykinase, angiotensinconverting enzyme and Xanthine oxidase, were selected as the target for the herein described project. (AU)

Scientific publications

(43)

(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)

ADRIANA F. L. VILELA; BÁRBARA M. FRUGERI; ANDRÉ L. F. SARRIA; RODRIGO O. S. KITAMURA; JOÃO B. FERNANDES; MARIA F. G. F. SILVA; QUEZIA B. CASS; CARMEN L. CARDOSO. Aminonaphthoquinone Mannich Bases Derived from Lawsone and Their Copper(II) Complex Derivatives: Synthesis and Potential Cholinesterase Inhibitors as Identified by On-flow Assay. Journal of the Brazilian Chemical Society, v. 27, n. 3, p. 534-545, 2016-03-00. (06/58043-3, 13/01710-1, 07/06393-3, 07/07196-7)

CALIL, FELIPE ANTUNES; LIMA, JULIANA MARIA; CAVALCANTE DE OLIVEIRA, ARTHUR HENRIQUE; MARIOTINI-MOURA, CHRISTIANE; RANGEL FIETTO, JULIANA LOPES; CARDOSO, CARMEN LUCIA. Immobilization of NTPDase-1 from Trypanosoma cruzi and Development of an Online Label-Free Assay. JOURNAL OF ANALYTICAL METHODS IN CHEMISTRY, 2016. (13/01710-1, 08/04371-5)

DE LIMA, BRUNA R.; LIMA, JULIANA M.; MACIEL, JESSICA B.; VALENTIM, CAROLINA Q.; NUNOMURA, RITA DE CSSIA S.; LIMA, EMERSON S.; KOOLEN, HECTOR H. F.; DE SOUZA, AFONSO DUARTE L.; PINHEIRO, MARIA LUCIA B.; CASS, QUEZIA B.; et al. Synthesis and Inhibition Evaluation of New Benzyltetrahydroprotoberberine Alkaloids Designed as Acetylcholinesterase Inhibitors. FRONTIERS IN CHEMISTRY, v. 7, SEP 18 2019. (14/50249-8, 13/01710-1)

LOPES VILELA, ADRIANA FERREIRA; CARDOSO, CARMEN LUCIA; MATEO, CESAR. An immobilized acetylcholinesterase as test system to screen new inhibitor drugs to treat Alzheimer's disease. SENSORS AND ACTUATORS B-CHEMICAL, v. 278, p. 196-201, JAN 1 2019. (16/15037-5, 13/01710-1)

LOPES, ADRIANA FERREIRA; CARDOSO, CARMEN LUCIA. An on-flow assay for screening of beta-secretase ligands by immobilised capillary reactor-mass spectrometry. ANALYTICAL METHODS, v. 9, n. 14, p. 2189-2196, APR 14 2017. (13/01710-1)

MAGALHAES, LUANA; CAVALCANTE DE OLIVEIRA, ARTHUR HENRIQUE; VASCONCELLOS, RAPHAEL DE SOUZA; MARIOTINI-MOURA, CHRISTIANE; FIRMINO, RAFAELA DE CASSIA; RANGEL FIETTO, JULIANA LOPES; CARDOSO, CARMEN LUCIA. Label-free assay based on immobilized capillary enzyme reactor of Leishmania infantum nucleoside triphosphate diphosphohydrolase (LicNTPDase-2-ICER-LC/UV). JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, v. 1008, p. 98-107, JAN 1 2016. (13/01710-1, 12/10749-6)

RODRIGUES DE MELO, RICARDO; CARLOS ALNOCH, ROBSON; LOPES VILELA, ADRIANA FERREIRA; DE SOUZA, EMANUEL MALTEMPI; KRIEGER, NADIA; RULLER, ROBERTO; SATO, HELIA HARUMI; MATEO, CESAR. New Heterofunctional Supports Based on Glutaraldehyde-Activation: A Tool for Enzyme Immobilization at Neutral pH. Molecules, v. 22, n. 7, JUL 2017. (13/01710-1, 16/15037-5)

RODRIGUES, M. V. N.; CORREA, R. S.; VANZOLINI, K. L.; SANTOS, D. S.; BATISTA, A. A.; CASS, Q. B.. Characterization and screening of tight binding inhibitors of xanthine oxidase: an on-flow assay. RSC ADVANCES, v. 5, n. 47, p. 37533-37538, 2015. (13/01710-1, 09/08131-1, 13/26559-4)

VANZOLINI, KENIA L.; VIEIRA, LUCAS C. C.; CORREA, ARLENE. G.; MOADDEL, RUIN; CASS, QUEZIA B.. Acetylcholinesterase immobilized on modified magnetic beads as a tool for screening a compound library. Microchimica Acta, v. 182, n. 13-14, p. 2209-2213, OCT 2015. (13/02054-0, 13/01710-1)

SEIDL, CLAUDIA; LOPES VILELA, ADRIANA FERREIRA; LIMA, JULIANA MARIA; LEME, GABRIEL MAZZI; CARDOSO, CARMEN LUCIA. A novel on-flow mass spectrometry-based dual enzyme assay. Analytica Chimica Acta, v. 1072, p. 81-86, SEP 23 2019. (13/01710-1, 14/50249-8)

AQUINO, AMANDA J.; ALVES, THAYANA DA C.; OLIVEIRA, V, REGINA; FERREIRA, ANTONIO G.; CASS, QUEZIA B.. Chemical secondary metabolite profiling of Bauhinia longifolia ethanolic leaves extracts. INDUSTRIAL CROPS AND PRODUCTS, v. 132, p. 59-68, JUN 2019. (13/01710-1)

GONCALVES NETO, GERALDO S.; DA COSTA, ROMARIO P.; ZANINI, CAMILA L.; AGUIAR, ANNA CAROLINE C.; DE SOUZA, JULIANA O.; DE SOUZA, GUILHERME E.; SEVERINO, RICHELE P.; CASS, QUEZIA B.; CRUZ, FABIO C.; OLIVA, GLAUCIUS; et al. Chemical Prospection of Qualea grandiflora Mart. Fruit and Stem Extracts and Their in vitro and in vivo Antiplasmodial Activity. Journal of the Brazilian Chemical Society, v. 31, n. 7, p. 1475-1484, JUL 2020. (13/01710-1, 13/07600-3)

LIMA, JULIANA M.; SEIDL, CLAUDIA; CUNHA, ELISE M. F.; OLIVEIRA, ARTHUR H. C.; CARDOSO, CARMEN L.. On-Flow Ligand Screening Assay Based on Immobilized Nucleoside Diphosphate Kinase B from Homo sapiens. Journal of the Brazilian Chemical Society, v. 30, n. 11, SI, p. 2308-2317, NOV 2019. (14/50249-8, 13/01710-1, 14/06907-0, 14/11640-3)

MANTOANI, SUSIMAIRE P.; CHIERRITO, TALITA P. C.; VILELA, ADRIANA F. L.; CARDOSO, CARMEN L.; MARTINEZ, ANA; CARVALHO, IVONE. Novel Triazole-Quinoline Derivatives as Selective Dual Binding Site Acetylcholinesterase Inhibitors. Molecules, v. 21, n. 2, FEB 2016. (13/50788-3, 13/01710-1, 12/14114-5, 12/04054-5)

IZADORA L. FURLANI; BRUNO S. AMARAL; REGINA V. OLIVEIRA; QUEZIA B. CASS. Imobilização enzimática: conceito e efeitos na proteólise. Química Nova, v. 43, n. 4, p. 463-473, 2020-06-10. (18/03035-3, 13/01710-1, 14/50249-8, 15/25755-0)

DE JESUS PRADO, VILMA MENEZES; DE JESUS, RAPHAEL AMANCIO; ANDRADE OLIVEIRA, JULIO MANOEL; BLANK, ARIE FITZGERALD; BEZERRA, DANIEL PEREIRA; PEREIRA SOARES, MILENA BOTELHO; SILVA, VALDENIZIA RODRIGUES; SANTOS, LUCIANO DE SOUZA; CARDOSO, CARMEN LUCIA; LOPES VILELA, ADRIANA FERREIRA; et al. Biological studies and chromatograms aided by chemometric analysis in evaluation of seasonality and extraction method of Croton grewioides extracts. Rev. bras. Bot., v. 45, n. 2, p. 12-pg., 2022-04-09. (14/50249-8, 14/11640-3, 13/01710-1)

DE LIMA, BRUNA R.; LIMA, JULIANA M.; MACIEL, JESSICA B.; VALENTIM, CAROLINA Q.; NUNOMURA, RITA DE CSSIA S.; LIMA, EMERSON S.; KOOLEN, HECTOR H. F.; DE SOUZA, AFONSO DUARTE L.; PINHEIRO, MARIA LUCIA B.; CASS, QUEZIA B.; et al. Synthesis and Inhibition Evaluation of New Benzyltetrahydroprotoberberine Alkaloids Designed as Acetylcholinesterase Inhibitors. RONTIERS IN CHEMISTR, v. 7, p. 12-pg., 2019-09-18. (13/01710-1, 14/50249-8)

SCATENA, GABRIEL S.; CASSIANO, NEILA M.; NETTO, CHAQUIP D.; COSTA, PAULO R. R.; CASS, QUEZIA B.; BATISTA, JOAO M., JR.. Preparative chiral separation and absolute configuration of the synthetic pterocarpanquinone LQB-118. CHIRALITY, v. 29, n. 5, p. 5-pg., 2017-05-01. (13/01710-1, 14/25222-9, 15/07089-2)

DE MORAES, MARCELA CRISTINA; CARDOSO, CARMEN LUCIA; CASS, QUEZIA BEZERRA. Solid-Supported Proteins in the Liquid Chromatography Domain to Probe Ligand-Target Interactions. RONTIERS IN CHEMISTR, v. 7, p. 16-pg., 2019-11-15. (13/01710-1, 14/50249-8)

VILELA, ADRIANA F. L.; FRUGERI, BARBARA M.; SARRIA, ANDRE L. F.; KITAMURA, RODRIGO O. S.; FERNANDES, JOAO B.; SILVA, MARIA F. G. F.; CASS, QUEZIA B.; CARDOSO, CARMEN L.. Aminonaphthoquinone Mannich Bases Derived from Lawsone and Their Copper( II) Complex Derivatives: Synthesis and Potential Cholinesterase Inhibitors as Identified by On-flow Assay. Journal of the Brazilian Chemical Society, v. 27, n. 3, p. 12-pg., 2016-03-01. (13/01710-1, 06/58043-3, 07/07196-7, 07/06393-3)

LOPES, BIANCA REBELO; BARREIRO, JULIANA CRISTINA; CASS, QUEZIA BEZERRA. Bioanalytical challenge: A review of environmental and pharmaceuticals contaminants in human milk. Journal of Pharmaceutical and Biomedical Analysis, v. 130, n. SI, p. 318-325, OCT 25 2016. (13/01710-1)

SCATENA, GABRIEL S.; CASSIANO, NEILA M.; NETTO, CHAQUIP D.; COSTA, PAULO R. R.; CASS, QUEZIA B.; BATISTA, JR., JOAO M.. Preparative chiral separation and absolute configuration of the synthetic pterocarpanquinone LQB-118. Chirality, v. 29, n. 5, p. 167-171, MAY 2017. (13/01710-1, 14/25222-9, 15/07089-2)

DE MORAES, MARCELA CRISTINA; CARDOSO, CARMEN LUCIA; CASS, QUEZIA BEZERRA. Solid-Supported Proteins in the Liquid Chromatography Domain to Probe Ligand-Target Interactions. FRONTIERS IN CHEMISTRY, v. 7, NOV 15 2019. (14/50249-8, 13/01710-1)

RAPHAEL A. DE JESUS; VILMA M. J. PRADO; VANDERSON S. PINTO; VALDENIZIA R. SILVA; LUCIANO S. SANTOS; PAULO C. L. NOGUEIRA; SANDRO NAVICKIENE; EDENIR R. PEREIRA-FILHO; ARIE F. BLANK; DANIEL P. BEZERRA; et al. Application of LC-DAD Metabolic Fingerprinting in Combination with PCA for Evaluation of Seasonality and Extraction Method on the Chemical Composition of Accessions from Lippia alba (Mill) N. E. Brown and Biological Activities. Journal of the Brazilian Chemical Society, v. 30, n. 5, p. 978-987, 2019-04-08. (13/01710-1, 14/11640-3)

LIMA, JULIANA MARIA; VIEIRA, PLINIO SALMAZO; CAVALCANTE DE OLIVEIRA, ARTHUR HENRIQUE; CARDOSO, CARMEN LUCIA. Label-free offline versus online activity methods for nucleoside diphosphate kinase b using high performance liquid chromatography. ANALYST, v. 141, n. 15, p. 4733-4741, 2016. (14/06907-0, 13/01710-1, 11/20569-2)

DE MORAES, MARCELA CRISTINA; CARDOSO, CARMEN LUCIA; SEIDL, CLAUDIA; MOADDEL, RUIN; CASS, QUEZIA BEZERRA. Targeting Anti-Cancer Active Compounds: Affinity-Based Chromatographic Assays. CURRENT PHARMACEUTICAL DESIGN, v. 22, n. 39, p. 5976-5987, 2016. (13/01710-1)

ALVIM-, JR., JOEL; LOPES, BIANCA REBELO; CASS, QUEZIA BEZERRA. Simultaneous enantioselective quantification of fluoxetine and norfluoxetine in human milk by direct sample injection using 2-dimensional liquid chromatography-tandem mass spectrometry. Journal of Chromatography A, v. 1451, p. 120-126, JUN 17 2016. (13/01710-1)

VANZOLINI, KENIA LOURENCO; AINSWORTH, STUART; BRUYNEEL, BEN; HERZIG, VOLKER; SERAUS, MITCHELL G. L.; SOMSEN, GOVERT W.; CASEWELL, NICHOLAS R.; CASS, QUEZIA BEZERRA; KOOL, JEROEN. Rapid ligand fishing for identification of acetylcholinesterase-binding peptides in snake venom reveals new properties of dendrotoxins. Toxicon, v. 152, p. 1-8, SEP 15 2018. (15/18504-0, 13/01710-1)

BATISTA, ANDREA N. L.; DOS SANTOS, JR., FERNANDO M.; BATISTA, JR., JOAO M.; CASS, QUEZIA B.. Enantiomeric Mixtures in Natural Product Chemistry: Separation and Absolute Configuration Assignment. Molecules, v. 23, n. 2, FEB 2018. (13/01710-1, 16/23794-0, 14/25222-9, 15/07089-2)

DE ALMEIDA, FERNANDO G.; VANZOLINI, KENIA L.; CASS, QUEZIA B.. Angiotensin converting enzyme immobilized on magnetic beads as a tool for ligand fishing. Journal of Pharmaceutical and Biomedical Analysis, v. 132, p. 159-164, JAN 5 2017. (13/01710-1, 11/00398-9)

RODRIGUES, MARILI V. N.; BARBOSA, ALEXANDRE F.; DA SILVA, JULIA F.; DOS SANTOS, DEBORAH A.; VANZOLINI, KENIA L.; DE MORAES, MARCELA C.; CORREA, ARLENE G.; CASS, QUEZIA B.. 9-Benzoyl 9-deazaguanines as potent xanthine oxidase inhibitors. Bioorganic & Medicinal Chemistry, v. 24, n. 2, p. 226-231, JAN 15 2016. (13/01710-1, 13/50680-8, 13/07600-3)

DO AMARAL, BRUNO S.; DA SILVA, LARISSA R. G.; VALVERDE, ALESSANDRA L.; DE SOUSA, LORENA R. F.; SEVERINO, RICHELE P.; DE SOUZA, DULCE H. F.; CASS, QUEZIA B.. Phosphoenolpyruvate carboxykinase from T. cruzi magnetic beads affinity-based screening assays on crude plant extracts from Brazilian Cerrado. Journal of Pharmaceutical and Biomedical Analysis, v. 193, JAN 30 2021. (13/01710-1, 14/50249-8)

VILMA M. J. PRADO; RAPHAEL A. DE JESUS; JULIO M. A. OLIVEIRA; CAMILA S. A. PEREIRA; ARIE F. BLANK; EDENIR R. PEREIRA-FILHO; QUEZIA B. CASS; JULIANA M. DE LIMA; ANTONIO G. FERREIRA; PAULO C. L. NOGUEIRA; et al. Evaluation of the Seasonality and Extraction Method on the Polar Extracts of Croton grewioides Baill. by Chromatogram Fingerprinting and Isolation of a New Triglycosylated Flavonoid. Journal of the Brazilian Chemical Society, v. 32, n. 2, p. 385-394, 2021-02-01. (14/11640-3, 13/01710-1)

DO AMARAL, BRUNO S.; CORREA, KATIA CELINA S.; CORREA, ARLENE G.; DE SOUZA, DULCE H. F.; CASS, QUEZIA B.. Direct Assay to Evaluate Phosphoenolpyruvate Carboxykinase Activity. Journal of the Brazilian Chemical Society, v. 30, n. 10, SI, p. 2105-2113, OCT 2019. (14/50249-8, 13/01710-1)

LOPES, BIANCA REBELO; BARREIRO, JULIANA CRISTINA; CASS, QUEZIA BEZERRA. Bioanalytical challenge: A review of environmental and pharmaceuticals contaminants in human milk. Journal of Pharmaceutical and Biomedical Analysis, v. 130, p. 8-pg., 2016-10-25. (13/01710-1)

CALIL, FELIPE ANTUNES; LIMA, JULIANA MARIA; CAVALCANTE DE OLIVEIRA, ARTHUR HENRIQUE; MARIOTINI-MOURA, CHRISTIANE; RANGEL FIETTO, JULIANA LOPES; CARDOSO, CARMEN LUCIA. Immobilization of NTPDase-1 from Trypanosoma cruzi and Development of an Online Label-Free Assay. JOURNAL OF ANALYTICAL METHODS IN CHEMISTRY, v. 2016, p. 9-pg., 2016-01-01. (13/01710-1, 08/04371-5)

MEDINA, REBECA P.; ARAUJO, ANGELA R.; BATISTA JR, JOAO M.; CARDOSO, CARMEN L.; SEIDL, CLAUDIA; VILELA, ADRIANA F. L.; DOMINGOS, V, HELORI; COSTA-LOTUFO, V, LETICIA; ANDERSEN, RAYMOND J.; SILVA, DULCE H. S.. Botryane terpenoids produced by Nemania bipapillata, an endophytic fungus isolated from red alga Asparagopsis taxiformis - Falkenbergia stage. SCIENTIFIC REPORTS, v. 9, AUG 23 2019. (13/01710-1, 14/50926-0, 15/17177-6, 13/07600-3)

DOS SANTOS, JR., FERNANDO M.; BICALHO, KEYLLA U.; CALISTO, ITALO H.; SCATENA, GABRIEL S.; FERNANDES, JOAO B.; CASS, QUEZIA B.; BATISTA, JR., JOAO M.. Scope of the 2(5H)-furanone helicity rule: a combined ECD, VCD, and DFT investigation. ORGANIC & BIOMOLECULAR CHEMISTRY, v. 16, n. 24, p. 4509-4516, JUN 28 2018. (15/07089-2, 13/01710-1, 14/25222-9, 10/18832-4, 12/25299-6, 16/23794-0)

SPRENGER, R. F.; THOMASI, S. S.; FERREIRA, A. G.; CASS, Q. B.; BATISTA JUNIOR, J. M.. Solution-state conformations of natural products from chiroptical spectroscopy: the case of isocorilagin. ORGANIC & BIOMOLECULAR CHEMISTRY, v. 14, n. 13, p. 3369-3375, 2016. (11/11021-3, 13/01710-1, 14/25222-9, 15/07089-2)

VANZOLINI, K. L.; SPRENGER, R. DA F.; LEME, G. M.; MORAES, V. R. DE S.; VILELA, A. F. L.; CARDOSO, C. L.; CASS, Q. B.. Acetylcholinesterase affinity-based screening assay on Lippia gracilis Schauer extracts. Journal of Pharmaceutical and Biomedical Analysis, v. 153, p. 232-237, MAY 10 2018. (13/02054-0, 13/01710-1, 16/24957-0, 14/50249-8)

CANZI, EDIONE F.; LOPES, BIANCA REBELO; ROBELDO, THAIANE; BORRA, RICARDO; DA SILVA, MARIA FATIMA G. F.; OLIVEIRA, V, REGINA; MAIA, BEATRIZ HELENA N. S.; CASS, QUEZIA B.. Prostaglandins E-2 and F-2 alpha levels in human menstrual fluid by online Solid Phase Extraction coupled to Liquid Chromatography tandem Mass Spectrometry (SPE-LC-MS/MS). JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, v. 1109, p. 60-66, MAR 1 2019. (13/01710-1)

DE JESUS, RAPHAEL A.; PRADO, VILMA M. J.; PINTO, VANDERSON S.; SILVA, VALDENIZIA R.; SANTOS, LUCIANO S.; NOGUEIRA, PAULO C. L.; NAVICKIENE, SANDRO; PEREIRA-FILHO, EDENIR R.; BLANK, ARIE E.; BEZERRA, DANIEL P.; et al. Application of LC-DAD Metabolic Fingerprinting in Combination with PCA for Evaluation of Seasonality and Extraction Method on the Chemical Composition of Accessions from Lippia alba (Mill.) N. E. Brown and Biological Activities. Journal of the Brazilian Chemical Society, v. 30, n. 5, p. 978-987, MAY 2019. (13/01710-1, 14/11640-3)

CORNELIO, VIVIAN ESTEVAM; DE MORAES, MARCELA CRISTINA; DOMINGUES, VANESSA DE CASSIA; FERNANDES, JOAO BATISTA; DAS GRACAS FERNANDES DA SILVA, MARIA FATIMA; CASS, QUEZIA BEZERRA; VIEIRA, PAULO CEZAR. Cathepsin D immobilized capillary reactors for on-flow screening assays. Journal of Pharmaceutical and Biomedical Analysis, v. 151, p. 252-259, MAR 20 2018. (13/01710-1, 09/17538-8)