Development of Fluorescent Probes for the Determination of Binding Sites on Albumin: Studies of the Relationship of the Molecular Structure, Association Constant and Specificity

• Grant number: 16/22014-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2017
• End date: May 31, 2021
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Valdecir Farias Ximenes
• Grantee: Luiza de Carvalho Bertozo
• Host Institution: Faculdade de Ciências (FC). Universidade Estadual Paulista (UNESP). Campus de Bauru. Bauru , SP, Brazil

Abstract

The human serum albumin, HSA, is a major protein constituent from blood plasma. Among its functions, it highlights its performance in the transport of drugs. This property is particularly relevant in the context pharmacokinetic, since the HSA-drug interaction may interfere with the bioavailability of the drug in the body, affecting its therapeutic action. Therefore, evaluate the interaction between drugs or other exogenous substances and the HSA is of great importance for the understanding of the pharmacokinetic characteristics. HSA has two major binding sites called site I and site II. The determination of the drug binding sites on HSA is done by the use of fluorescent probes that bind to these sites. Recent studies in our research group, as well as a critical survey of the results presented in the literature, revealed inconsistencies in the application of site I dansyl probes, which has lead to misinterpretations of the substances studied characteristics with respect to the albumin binding site. Therefore, this project aims to study and synthesis of new dansyl amino acids that can help to elucidate the binding sites of drugs in HSA. Specifically, it is intended to characterize the interaction parameters including binding constants (spectroscopic and calorimetric techniques), characterization of the sites by competitive studies, interaction studies by induced circular dichroism, molecular dynamics studies, among others. As models will use the dansyl amino acids dansilados dansylamide, dansylarginine and dansylisine to the site I and dansylproline, dansylnorleucine and dansylserine to site II. With the results with these compounds will be proposed structural changes that lead to new dansyl compounds with greater specificity to the site I of HSA.

Scientific publications

(7)

(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)

BERTOZO, LUIZA DE CARVALHO; NETO, ERNESTO TAVARES; DE OLIVEIRA, LEANDRO CRISTANTE; XIMENES, VALDECIR FARIAS. Oxidative Alteration of Trp-214 and Lys-199 in Human Serum Albumin Increases Binding Affinity with Phenylbutazone: A Combined Experimental and Computational Investigation. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 19, n. 10, OCT 2018. (14/50926-0, 16/20549-5, 16/22014-1)

DE VASCONCELOS, DEBORA NALIATI; LIMA, ANGELICA NAKAGAWA; PHILOT, ERIC ALLISON; SCOTT, ANA LIGIA; FERREIRA BOZA, IZABELLE AMORIM; DE SOUZA, AGUINALDO ROBINSON; MORGON, NELSON HENRIQUE; XIMENES, VALDECIR FARIAS. Methyl divanillate: redox properties and binding affinity with albumin of an antioxidant and potential NADPH oxidase inhibitor. RSC ADVANCES, v. 9, n. 35, p. 19983-19992, JUL 1 2019. (14/50926-0, 16/20549-5, 16/22014-1)

BERTOZO, LUIZA DE CARVALHO; MASZOTA-ZIELENIAK, MARTYNA; BOLEAN, MAYTE; CIANCAGLINI, PIETRO; SAMSONOV, SERGEY A.; XIMENES, VALDECIR F.. inding of fluorescent dansyl amino acids in albumin: When access to the protein cavity is more important than the strength of bindin. DYES AND PIGMENTS, v. 188, APR 2021. (19/18445-5, 16/22014-1)

DE CARVALHO BERTOZO, LUIZA; FERNANDES, ANA J. F. C.; YOGUIM, MAURICIO I.; BOLEAN, MAYTE; CIANCAGLINI, PIETRO; XIMENES, VALDECIR F.. Entropy-driven binding of octyl gallate in albumin: Failure in the application of temperature effect to distinguish dynamic and static fluorescence quenching. JOURNAL OF MOLECULAR RECOGNITION, v. 33, n. 7, MAR 2020. (14/50926-0, 16/20549-5, 16/22014-1)

BERTOZO, LUIZA DE CARVALHO; PHILOT, ERIC ALLISON; LIMA, ANGELICA NAKAGAWA; DE RESENDE LARA, PEDRO TULIO; SCOTT, ANA LIGIA; XIMENES, VALDECIR FARIAS. Interaction between 1-pyrenesulfonic acid and albumin: Moving inside for the protein. SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY, v. 208, p. 243-254, FEB 5 2019. (14/50926-0, 16/22014-1, 16/20549-5)

BERTOZO, LUIZA DE CARVALHO; MASZOTA-ZIELENIAK, MARTYNA; BOLEAN, MAYTE; CIANCAGLINI, PIETRO; SAMSONOV, SERGEY A.; XIMENES, VALDECIR F.. Binding of fluorescent dansyl amino acids in albumin: When access to the protein cavity is more important than the strength of binding. DYES AND PIGMENTS, v. 188, p. 13-pg., 2021-02-08. (19/18445-5, 16/22014-1)

BERTOZO, LUIZA DE CARVALHO; NETO, ERNESTO TAVARES; DE OLIVEIRA, LEANDRO CRISTANTE; XIMENES, VALDECIR FARIAS. Oxidative Alteration of Trp-214 and Lys-199 in Human Serum Albumin Increases Binding Affinity with Phenylbutazone: A Combined Experimental and Computational Investigation. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 19, n. 10, p. 17-pg., 2018-10-01. (14/50926-0, 16/20549-5, 16/22014-1)

Academic Publications

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

BERTOZO, Luiza de Carvalho. Development of fluorescent probes for determination of binding sites in albumin: study of the relationship between molecular structure, association constant and specificity. 2021. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Ciências. Bauru Bauru.