Advanced search
Start date
Betweenand

Synthesis, kinetic studies and applications of substrates and inhibitors for proteolytic enzymes

Grant number: 12/50191-4
Support type:Research Projects - Thematic Grants
Duration: December 01, 2012 - November 30, 2018
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Maria Aparecida Juliano
Grantee:Maria Aparecida Juliano
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated grant(s):18/13588-0 - Multi - user equipment approved in grant 2012/50191-4: mass spectrometer impact II - Bruker, AP.EMU
Associated scholarship(s):15/01829-4 - Human tissue kallikrein (KLK1) and human plasma kallikrein on metabolism of semaphorins and neurotrophins, BP.PD
14/18877-9 - Proteolytic enzymes in skin physiology and pathophysiology, BP.PD
14/18451-1 - Leptospira spp. strains database implemention by MALDI-TOF-MS and activity analysis of their secreted proteases, BP.IC
+ associated scholarships 13/21455-6 - Applied study will bioanalytical search profile blood plasma amino acid carriers Syndrome Cri-Du-Chat, BP.MS
13/07763-0 - Studies of radical acetylation of proteins using proteomics tools, BP.DR
13/12106-8 - Screening and characterization of serine carboxyl peptidases and glutamic peptidases in bacteria isolated from the composting operation at the São Paulo Zoo Park, BP.PD
13/06654-2 - Synthesis and functionalization of mesoporous silicas aiming application bioanalytical, BP.IC
11/20941-9 - Development and use of fluorescence techniques for the study of protein conformational changes, BP.PD - associated scholarships

Abstract

Considerable progress in the study of proteases was based on the development of synthetic peptides, which resulted in the chromogenic and fluorescent substrates. Quenched fluorescent peptides based on the transfer of energy by resonance of a fluorescent to a quancher group was the more recent and significant progress in the field that we are involve since 1990's. The synthesis of these FRET (Fluorescence Resonance Energy Transfer) peptides in solid phase linked to flexible resins and in systems of parallel synthesis allowed us to study the substrate specificity of several proteases by systematic variations in all positions of peptides with up to 10 amino acids in length. The project presented here is based on the development of modern techniques of organic synthesis and protein biochemistry for study of proteases involved in physiological and pathological processes. The proposals of this project are: Synthesis and assays with proteases of FRET peptide libraries in solid phase and in solution. Synthesis of protease inhibitors using non-natural amino acids. Assays as protease inhibitors of tellurium organic compounds and nitroolefins, particularly the cysteine proteases. Systematic studies will be done with human kallikreins, Plamodium and Leishmania proteases, processing peptidases and oligopeptidases. Virus, fungi and bactéria proteases were also included. (AU)

Articles published in Agência FAPESP Newsletter about the research grant
Brazilian scientists explain how pineapple stem bromelain relieves pain 
Articles published in other media outlets (38 total):
More itemsLess items
Brazilian Scientists Explain How Pineapple Stem Bromelain Relieves Pain 
Desvelan el efecto analgésico de la bromelina del ananá 
Científicos desvelan el efecto analgésico de la bromelina del ananá 
Pesquisadores brasileiros descobrem propriedade analgésica no abacaxi 
Efeito analgésico do abacaxi é desvendado por pesquisadores brasileiros 
Cientistas brasileiros descobrem efeito analgésico em abacaxi 
Cientistas brasileiros descobrem efeito analgésico em abacaxi 
Pesquisadores brasileiros desvendam ação analgésica do abacaxi 
Cientistas brasileiros descobrem efeito Analgésico em Abacaxi! 
Cientistas brasileiros descobrem efeito analgésico em abacaxi 
Cientistas brasileiros descobrem efeito analgésico em abacaxi 
Cientistas brasileiros descobrem efeito analgésico em abacaxi 
Cientistas brasileiros descobrem efeito analgésico em abacaxi 
Efeito analgésico da bromelina do abacaxi é desvendado 
Cientistas brasileiros descobrem efeito analgésico em abacaxi 
Enzima do abacaxi pode ser um caminho para controlar a dor 
Abacaxi analgésico 
Abacaxi tem efeito analgésico? Cientistas desvendam ação de enzima 
Efeito analgésico da bromelina do abacaxi é desvendado 
Efeito analgésico da bromelina do abacaxi é desvendado 
Efeito analgésico da bromelina do abacaxi é desvendado 
Efeito analgésico da bromelina do abacaxi é desvendado 
Efeito analgésico da bromelina do abacaxi é desvendado 
Pesquisadores desvendam o efeito analgésico da enzima bromelina encontrada no abacaxi 
Pesquisadores brasileiros desvendam efeito analgésico presente no abacaxi 
Pesquisadores brasileiros desvendam efeito analgésico presente no abacaxi 
Efeito analgésico da bromelina do abacaxi é desvendado 
Efeito analgésico da bromelina do abacaxi é desvendado 
Efeito analgésico do abacaxi é desvendado por pesquisadores brasileiros 
Efeito analgésico da bromelina do abacaxi é desvendado 
Efeito analgésico da bromelina do abacaxi é desvendado 
Efeito analgésico da bromelina do abacaxi é desvendado 
Efeito analgésico da bromelina do abacaxi é desvendado 
Efeito analgésico da bromelina do abacaxi é desvendado 
Efeito analgésico da bromelina do abacaxi é desvendado em estudo apoiado pela Fapesp 
Efeito analgésico da bromelina do abacaxi é desvendado 
Pesquisadores brasileiros desvendam efeito analgésico presente no abacaxi 
Pesquisadores brasileiros desvendam efeito analgésico presente no abacaxi 

Scientific publications (23)
(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)
RIBEIRO GOMES MAIA, ANA CAROLINA; PORCINO, GABRIANE NASCIMENTO; FARIA-PINTO, PRISCILA; MENDES, TULIO VIEIRA; RIBEIRO ANTINARELLI, LUCIANA MARIA; COIMBRA, ELAINE SOARES; REIS, ALEXANDRE BARBOSA; JULIANO, LUIZ; JULIANO, MARIA APARECIDA; MARQUES, MARCOS JOSE; VASCONCELOS, EVELINE GOMES. Leishmania infantum nucleoside triphosphate diphosphohydrolase 1 (NTPDase 1) B-domain: Antibody antiproliferative effect on the promastigotes and IgG subclass responses in canine visceral leishmaniasis. Veterinary Parasitology, v. 271, p. 38-44, JUL 2019. Web of Science Citations: 0.
ORLANDI-MATTOS, PAULO EDUARDO; AGUIAR, RODRIGO BARBOSA; VAZ JUNIOR, ITABAJARA DA SILVA; MORAES, JANE ZVEITER; DE ARAUJO CARLINI, ELISALDO LUIZ; JULIANO, MARIA APARECIDA; JULIANO, LUIZ. Enkephalin related peptides are released from jejunum wall by orally ingested bromelain. Peptides, v. 115, p. 32-42, MAY 2019. Web of Science Citations: 0.
RAMOS, PATRICIA L.; KONDO, MARCIA Y.; SANTOS, SAARA M. B.; DE VASCONCELLOS, SUZAN P.; ROCHA, RAFAEL C. S.; DA CRUZ, JOAO B.; EUGENIO, PATRICIA F. M.; CABRAL, HAMILTON; JULIANO, MARIA A.; JULIANO, LUIZ; SETUBAL, JOAO C.; DA SILVA, ALINE M.; CAPPELINI, LUCIANA T. D. A Tropical Composting Operation Unit at SAo Paulo Zoo as a Source of Bacterial Proteolytic Enzymes. Applied Biochemistry and Biotechnology, v. 187, n. 1, p. 282-297, JAN 2019. Web of Science Citations: 2.
KARCHER, DANIEL; GRENFELL, RAFAELLA C.; MORENO, ANDREA MICKE; MORENO, LUISA ZANOLLI; VASCONCELLOS, SILVIO ARRUDA; HEINEMANN, MARCOS B.; DE ALMEIDA JUNIOR, JOAO N.; JULIANO, LUIZ; JULIANO, MARIA A. Identification of pathogenic and nonpathogenic Leptospira species of Brazilian isolates by Matrix Assisted Laser Desorption/Ionization and Time Flight mass spectrometry. Brazilian Journal of Microbiology, v. 49, n. 4, p. 900-908, OCT-DEC 2018. Web of Science Citations: 0.
JOCELINO GOMES DE LACERDA, JOSE THALLES; RODRIGUES E LACERDA, RODRIGO; ASSUNCAO, NILSON ANTONIO; TASHIMA, ALEXANDRE KEIJI; JULIANO, MARIA APARECIDA; DOS SANTOS, JR., GILBERTO ALVES; DE SOUZA, MILENY DOS SANTOS; BATISTA, JACINTO DE LUNA; ROSSI, CARLOS EDUARDO; DE ALMEIDA GADELHA, CARLOS ALBERTO; SANTI-GADELHA, TATIANE. New insights into lectin from Abelmoschus esculentus seeds as a Kunitz-type inhibitor and its toxic effects on Ceratitis capitata and root-knot nematodes Meloidogyne spp.. Process Biochemistry, v. 63, p. 96-104, DEC 2017. Web of Science Citations: 0.
SILVA, ROBERTA N.; OLIVEIRA, LILIAN C. G.; PARISE, CAROLINA B.; OLIVEIRA, JULIANA R.; SEVERINO, BEATRICE; CORVINO, ANGELA; DI VAIO, PAOLA; TEMUSSI, PIERO A.; CALIENDO, GIUSEPPE; SANTAGADA, VINCENZO; JULIANO, LUIZ; JULIANO, MARIA A. Activity of human kallikrein-related peptidase 6 (KLK6) on substrates containing sequences of basic amino acids. Is it a processing protease?. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1865, n. 5, p. 558-564, MAY 2017. Web of Science Citations: 2.
SONG, EUN SUK; JANG, HYEIN; GUO, HOU-FU; JULIANO, MARIA A.; JULIANO, LUIZ; MORRIS, ANDREW J.; GALPERIN, EMILIA; RODGERS, DAVID W.; HERSH, LOUIS B. Inositol phosphates and phosphoinositides activate insulin-degrading enzyme, while phosphoinositides also mediate binding to endosomes. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 114, n. 14, p. E2826-E2835, APR 4 2017. Web of Science Citations: 5.
GILIO, JOYCE M.; MARCONDES, MARCELO F.; FERRARI, DEBORA; JULIANO, MARIA A.; JULIANO, LUIZ; OLIVEIRA, VITOR; MACHADO, MAURICIO F. M. Processing of metacaspase 2 from Trypanosoma brucei (TbMCA2) broadens its substrate specificity. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1865, n. 4, p. 388-394, APR 2017. Web of Science Citations: 5.
INDARTE, MARTIN; LAZZA, CRISTIAN M.; ASSIS, DIEGO; CAFFINI, NESTOR O.; JULIANO, MARIA A.; AVILES, FRANCESC X.; DAURA, XAVIER; LOPEZ, LAURA M. I.; TREJO, SEBASTIAN A. A Bowman-Birk protease inhibitor purified, cloned, sequenced and characterized from the seeds of Maclura pomifera (Raf.) Schneid. PLANTA, v. 245, n. 2, p. 343-353, FEB 2017. Web of Science Citations: 0.
REISS-PISTILLI, MARIA L. V.; SCHUPPAN, DETLEF; BARROSO, MADALENA M. S.; ASSUNCAO-MIRANDA, IRANAIA; FARIAS, SHIRLEY; LERY, LETICIA; BAUER, MICHAEL; JULIANO, LUIZ; JULIANO, MARIA A.; COELHO-SAMPAIO, TATIANA. An extracellular proteasome releases endostatin from human collagen XVIII. ANGIOGENESIS, v. 20, n. 1, p. 125-137, FEB 2017. Web of Science Citations: 1.
KONDO, MARCIA Y.; GOUVEA, IURI E.; OKAMOTO, DEBORA N.; SANTOS, JORGE A. N.; SOUCCAR, CADEN; ODA, KOHEI; JULIANO, LUIZ; JULIANO, MARIA A. Analysis of catalytic properties of tripeptidyl peptidase I (TTP-I), a serine carboxyl lysosomal protease, and its detection in tissue extracts using selective FRET peptide substrate. Peptides, v. 76, p. 80-86, FEB 2016. Web of Science Citations: 0.
ASSIS, DIEGO M.; JULIANO, LUIZ; PASCHOALIN, THAYSA; KOUYOUMDJIAN, MARIA; CALIXTO, JOAO B.; SANTOS, ROBSON A. S.; PERTINHEZ, THELMA A.; GAUTHIER, FRANCIS; MOREAU, THIERRY; BLABER, MICHAEL; JULIANO, MARIA A. Pharmacological Activities and Hydrolysis by Peptidases of [Phospho-Ser(6)]-Bradykinin (pS(6)-BK). Biochemical Pharmacology, v. 97, n. 2, p. 203-214, SEP 15 2015. Web of Science Citations: 2.
ABREU, AFONSO G.; FRAGA, TATIANA R.; GRANADOS MARTINEZ, ADRIANA P.; KONDO, MARCIA Y.; JULIANO, MARIA A.; JULIANO, LUIZ; NAVARRO-GARCIA, FERNANDO; ISAAC, LOURDES; BARBOSA, ANGELA S.; ELIAS, WALDIR P. The Serine Protease Pic From Enteroaggregative Escherichia coli Mediates Immune Evasion by the Direct Cleavage of Complement Proteins. Journal of Infectious Diseases, v. 212, n. 1, p. 106-115, JUL 1 2015. Web of Science Citations: 17.
OLIVEIRA, JULIANA R.; BERTOLIN, THIAGO C.; ANDRADE, DOUGLAS; OLIVEIRA, LILIAN C. G.; KONDO, MARCIA Y.; SANTOS, JORGE A. N.; BLABER, MICHAEL; JULIANO, LUIZ; SEVERINO, BEATRICE; CALIENDO, GIUSEPPE; SANTAGADA, VINCENZO; JULIANO, MARIA A. Specificity studies on Kallikrein-related peptidase 7 (KLK7) and effects of osmolytes and glycosaminoglycans on its peptidase activity. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1854, n. 1, p. 73-83, JAN 2015. Web of Science Citations: 15.
SEVERINO, BEATRICE; FIORINO, FERDINANDO; CORVINO, ANGELA; CALIENDO, GIUSEPPE; SANTAGADA, VINCENZO; ASSIS, DIEGO MAGNO; OLIVEIRA, JULIANA R.; JULIANO, LUIZ; MANGANELLI, SERENA; BENFENATI, EMILIO; FRECENTESE, FRANCESCO; PERISSUTTI, ELISA; JULIANO, MARIA APARECIDA. Synthesis, biological evaluation, and docking studies of PAR2-AP-derived pseudopeptides as inhibitors of kallikrein 5 and 6. Biological Chemistry, v. 396, n. 1, p. 45-52, JAN 2015. Web of Science Citations: 4.
HAMIN NETO, YOUSSEF A. A.; DE OLIVEIRA, LILIAN C. G.; DE OLIVEIRA, ARTHUR H. C.; ROSA, JOSE C.; JULIANO, MARIA A.; JULIANO, LUIZ; RODRIGUES, ANDRE; CABRAL, HAMILTON. Determination of Specificity and Biochemical Characteristics of Neutral Protease Isolated from Myceliophthora thermophila. PROTEIN AND PEPTIDE LETTERS, v. 22, n. 11, p. 972-982, 2015. Web of Science Citations: 6.
MARCONDES, M. F. M.; ALVES, F. M.; ASSIS, D. M.; HIRATA, I. Y.; JULIANO, L.; OLIVEIRA, V.; JULIANO, M. A. Substrate specificity of mitochondrial intermediate peptidase analysed by a support-bound peptide library. FEBS OPEN BIO, v. 5, p. 429-436, 2015. Web of Science Citations: 1.
STEINBERGER, JUTTA; GRISHKOVSKAYA, IRINA; CENCIC, REGINA; JULIANO, LUIZ; JULIANO, MARIA A.; SKERN, TIM. Foot-and-mouth disease virus leader proteinase: Structural insights into the mechanism of intermolecular cleavage. VIROLOGY, v. 468, p. 397-408, NOV 2014. Web of Science Citations: 10.
OLIVEIRA, LILIAN C. G.; OKAMOTO, DEBORA N.; OLIVEIRA, JULIANA R.; KONDO, MARCIA Y.; GOUVEA, IURI E.; BITEAU, NICOLAS; BALTZ, THEO; MURAKAMI, MARIO T.; JULIANO, LUIZ; JULIANO, MARIA A. Analysis of peptidase activities of a cathepsin B-like (TcoCBc1) from Trypanosoma congolense. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1844, n. 7, p. 1260-1267, JUL 2014. Web of Science Citations: 1.
DE SOUZA, EDUARDO SERGIO; KATAGIRI, ALBERTO H.; JULIANO, LUIZ; JULIANO, MARIA APARECIDA; PIMENTA, DANIEL CARVALHO; ITO, AMANDO SIUITI. Fret Studies of Conformational Changes in Heparin-Binding Peptides. Journal of Fluorescence, v. 24, n. 3, p. 885-894, MAY 2014. Web of Science Citations: 2.
PEREIRA, FELIPE V.; FERREIRA-GUIMARAES, CARLA A.; PASCHOALIN, THAYSA; SCUTTI, JORGE A. B.; MELO, FILIPE M.; SILVA, LUIS S.; MELO, AMANDA C. L.; SILVA, PRISCILA; TIAGO, MANOELA; MATSUO, ALISSON L.; JULIANO, LUIZ; JULIANO, MARIA A.; CARMONA, ADRIANA K.; TRAVASSOS, LUIZ R.; RODRIGUES, ELAINE G. A Natural Bacterial-Derived Product, the Metalloprotease Arazyme, Inhibits Metastatic Murine Melanoma by Inducing MMP-8 Cross-Reactive Antibodies. PLoS One, v. 9, n. 4 APR 30 2014. Web of Science Citations: 4.
OKAMOTO, DEBORA N.; KONDO, MARCIA Y.; OLIVEIRA, LILIAN C. G.; HONORATO, RODRIGO V.; ZANPHORLIN, LETICIA M.; CORONADO, MONIKA A.; ARAUJO, MARIANA S.; DA MOTTA, GUACYARA; VERONEZ, CAMILA L.; ANDRADE, SHEILA S.; OLIVEIRA, PAULO S. L.; ARNI, RAGHUVIR K.; CINTRA, ADELIA C. O.; SAMPAIO, SUELY V.; JULIANO, MARIA A.; JULIANO, LUIZ; MURAKAMI, MARIO T.; GOUVEA, IURI E. P-I class metalloproteinase from Bothrops moojeni venom is a post-proline cleaving peptidase with kininogenase activity: Insights into substrate selectivity and kinetic behavior. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1844, n. 3, p. 545-552, MAR 2014. Web of Science Citations: 3.
OLIVEIRA, JOCELIA P. C.; FREITAS, RENATO F.; DE MELO, LEANDRO SILVA; BARROS, THALITA G.; SANTOS, JORGE A. N.; JULIANO, MARIA A.; PINHEIRO, SERGIO; BLABER, MICHAEL; JULIANO, LUIZ; MURI, ESTELA M. F.; PUZER, LUCIANO. Isomannide-Based Peptidomimetics as Inhibitors for Human Tissue Kallikreins 5 and 7. ACS Medicinal Chemistry Letters, v. 5, n. 2, p. 128-132, FEB 2014. Web of Science Citations: 21.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.
Filed patent(s) as a result of this research project

MÉTODO DE IDENTIFICAÇÃO DE COMPOSTOS ANTIVIRAIS, COMPOSTOS ANTIVIRAIS, MÉTODO DE AVALIAÇÃO DA FUNCIONALIDADE DOS COMPOSTOS ANTIVIRAIS, USO DOS COMPOSTOS ANTIVIRAIS E COMPOSIÇÃO FARMACÊUTICA ANTIVIRAL BR1020150065612 - Universidade de São Paulo (USP) ; Universidade Federal de São Paulo (UNIFESP) . Antonia Tavares do Amaral; Erika Piccirillo; Maria Aparecida Juliano; Marcia Yuri Kondo - March 2015, 24