Rodrigo da Silva Ferreira
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Previous Organizations / Institutes
The organizations / institutes from the scholar's other articles in the past ten years
Research Subjects
Rodrigo da Silva Ferreira has a total of 161 co-authors. Here are the top co-authors by number of shared publications:
- Maria Luiza Vilela Oliva
Departamento de Bioquímica, Universidade Federal de São Paulo (UNIFESP), São Paulo 04039-002, Brazil
20 shared publications - Patrícia Maria Guedes Paiva
Departamento de Bioquímica, Centro de Biociências Universidade Federal de Pernambuco Recife Brazil
12 shared publications - Thiago Henrique Napoleão
Departamento de Bioquímica, Centro de Biociências, Universidade Federal de Pernambuco, Recife 50670-420, PE, Brazil
7 shared publications - Alioscka A. Sousa
Federal University of São Paulo (UNIFESP)
5 shared publications André L. Lira
Department of Biochemistry, Federal University of São Paulo, São Paulo, Brazil
4 shared publications- Fabricio Pereira Batista
Department of Biochemistry Federal University of São Paulo (UNIFESP), Brazil
3 shared publications
Latest Publications
- Open Access
- 30 July 2026
- Published by Editora RECIMA21 LTDA in RECIMA21 - Revista Científica Multidisciplinar
- Vol. 7 (8) , e788642
HÁBITOS ALIMENTARES COMO ESTRATÉGIA DE PREVENÇÃO PRIMÁRIA DAS DOENÇAS CRÔNICAS NÃO TRANSMISSÍVEIS
Introducción: Las enfermedades crónicas no transmisibles (ECNT) representan uno de los principales desafíos para la salud pública mundial y están estrechamente relacionadas con los hábitos alimentarios y el estilo de vida. Objetivo: Analizar la evidencia científica sobre la influencia de los hábitos alimentarios en la prevención primaria de las ECNT, destacando los patrones dietéticos protectores, los factores asociados con la adherencia y los desafíos para la implementación de políticas públicas de nutrición. Métodos: Se realizó una revisión integradora de la literatura, guiada por la pregunta: ¿cuál es la influencia de los hábitos alimentarios en la prevención de las ECNT? Se consultaron las bases de datos MEDLINE/PubMed, LILACS y SciELO, incluyendo estudios publicados entre 2020 y 2025 en portugués, inglés y español. Tras aplicar los criterios de inclusión y exclusión, se seleccionaron 19 artículos para el análisis. Resultados: Los estudios evidenciaron asociaciones consistentes entre patrones alimentarios saludables, especialmente las dietas Mediterránea y DASH, y mejores indicadores metabólicos, inflamatorios y psicosociales, además de una reducción del riesgo de ECNT. Factores socioeconómicos, culturales y ambientales influyeron significativamente en la adherencia a una alimentación saludable. Conclusión: La promoción de hábitos alimentarios saludables constituye una estrategia esencial para la prevención primaria de las ECNT, requiriendo acciones educativas, políticas públicas integradas y entornos alimentarios que favorezcan elecciones saludables.
- 30 July 2026
- Published by Editora RECIMA21 LTDA in RECIMA21 - Revista Científica Multidisciplinar
- Vol. 7 (8) , e788642
Open AccessHÁBITOS ALIMENTARES COMO ESTRATÉGIA DE PREVENÇÃO PRIMÁRIA DAS DOENÇAS CRÔNICAS NÃO TRANSMISSÍVEIS
Introducción: Las enfermedades crónicas no transmisibles (ECNT) representan uno de los principales desafíos para la salud pública mundial y están estrechamente relacionadas con los hábitos alimentarios y el estilo de vida. Objetivo: Analizar la evidencia científica sobre la influencia de los hábitos alimentarios en la prevención primaria de las ECNT, destacando los patrones dietéticos protectores, los factores asociados con la adherencia y los desafíos para la implementación de políticas públicas de nutrición. Métodos: Se realizó una revisión integradora de la literatura, guiada por la pregunta: ¿cuál es la influencia de los hábitos alimentarios en la prevención de las ECNT? Se consultaron las bases de datos MEDLINE/PubMed, LILACS y SciELO, incluyendo estudios publicados entre 2020 y 2025 en portugués, inglés y español. Tras aplicar los criterios de inclusión y exclusión, se seleccionaron 19 artículos para el análisis. Resultados: Los estudios evidenciaron asociaciones consistentes entre patrones alimentarios saludables, especialmente las dietas Mediterránea y DASH, y mejores indicadores metabólicos, inflamatorios y psicosociales, además de una reducción del riesgo de ECNT. Factores socioeconómicos, culturales y ambientales influyeron significativamente en la adherencia a una alimentación saludable. Conclusión: La promoción de hábitos alimentarios saludables constituye una estrategia esencial para la prevención primaria de las ECNT, requiriendo acciones educativas, políticas públicas integradas y entornos alimentarios que favorezcan elecciones saludables.
- Open Access
- 26 July 2026
- Published by Wiley in Chemistry & Biodiversity
- Vol. 23 (7) , e71532
Integrated Approach for the Discovery of Antifungal and Antibiofilm Agents From Cerrado Plants
The increasing incidence of Candida albicans infections, especially those involving drug‐resistant strains, highlights the need for new antifungal agents. In this study, 108 plant extracts from native and endemic species of the Brazilian Cerrado were screened against C. albicans in both planktonic and biofilm forms (developing and mature). Eighteen extracts demonstrated significant antifungal and antibiofilm activity, particularly from species in the Fabaceae, Myrtaceae, and Celastraceae families. Extracts from Hymenaea stigonocarpa notably inhibited the yeast‐to‐hyphae transition, a key virulence factor. Using molecular networking (GNPS) and in silico tools (SIRIUS), 60 putative compounds were annotated, including xanthones, flavonoids and triterpenoids, with selected candidates showing favorable binding profiles in molecular docking analyses. This integrative metabolomic approach enabled the identification of bioactive scaffolds, reinforcing the Cerrado biome as a valuable source of structurally diverse metabolites for antifungal drug discovery.
- 26 July 2026
- Published by Wiley in Chemistry & Biodiversity
- Vol. 23 (7) , e71532
Open AccessIntegrated Approach for the Discovery of Antifungal and Antibiofilm Agents From Cerrado Plants
The increasing incidence of Candida albicans infections, especially those involving drug‐resistant strains, highlights the need for new antifungal agents. In this study, 108 plant extracts from native and endemic species of the Brazilian Cerrado were screened against C. albicans in both planktonic and biofilm forms (developing and mature). Eighteen extracts demonstrated significant antifungal and antibiofilm activity, particularly from species in the Fabaceae, Myrtaceae, and Celastraceae families. Extracts from Hymenaea stigonocarpa notably inhibited the yeast‐to‐hyphae transition, a key virulence factor. Using molecular networking (GNPS) and in silico tools (SIRIUS), 60 putative compounds were annotated, including xanthones, flavonoids and triterpenoids, with selected candidates showing favorable binding profiles in molecular docking analyses. This integrative metabolomic approach enabled the identification of bioactive scaffolds, reinforcing the Cerrado biome as a valuable source of structurally diverse metabolites for antifungal drug discovery.
- Open Access
- 3 February 2025
- Published by Brazilian Journals in Contribuciones A Las Ciencias Sociales
- Vol. 18 (2) , e15378
O uso de Isotretinoína no tratamento da acne severa: avaliação do risco de depressão e outras alterações psiquiátricas
A acne severa é uma condição dermatológica que afeta negativamente a qualidade de vida dos pacientes, tanto fisicamente quanto emocionalmente. Quando tratamentos convencionais não são eficazes, a isotretinoína é uma alternativa frequentemente utilizada. Embora sua eficácia no tratamento da acne severa seja comprovada, seu uso tem sido associado a efeitos adversos na saúde mental, incluindo depressão, ansiedade e ideação suicida, levantando preocupações sobre a relação entre o medicamento e distúrbios psiquiátricos. O objetivo geral deste estudo é compreender os efeitos psicológicos do uso da isotretinoína no tratamento de acne severa, com foco no desenvolvimento de sintomas como depressão, ansiedade e ideação suicida. Os objetivos específicos incluem investigar o impacto da isotretinoína na saúde mental, explorar os mecanismos químicos relacionados a alterações de humor e sugerir estratégias de monitoramento e apoio emocional durante o tratamento. Este estudo consistE em uma revisão sistemática da literatura, conduzida por meio de bases de dados como PubMed, Scopus e Web of Science. Foram analisados artigos publicados entre 2010 e 2025 que investigaram a relação entre isotretinoína e transtornos psiquiátricos. A pesquisa seguiu as diretrizes PRISMA e incluiu estudos observacionais e ensaios clínicos randomizados. Os resultados indicam que, embora a isotretinoína seja altamente eficaz no tratamento da acne severa, seu uso pode estar relacionado ao agravamento de sintomas psiquiátricos, especialmente em indivíduos com vulnerabilidade emocional. Estudos mostram que alterações nos níveis de neurotransmissores como serotonina e dopamina podem ser um fator contribuidor. No entanto, a relação exata entre o medicamento e os distúrbios psiquiátricos ainda não é totalmente compreendida. O uso de isotretinoína, embora eficaz no tratamento da acne severa, deve ser acompanhado de cuidados psicológicos rigorosos. Pacientes com histórico de distúrbios emocionais devem ser monitorados de perto, e a administração do medicamento deve ser ajustada conforme a necessidade. A colaboração multidisciplinar é essencial para garantir que os benefícios dermatológicos do tratamento não sejam superados pelos riscos psiquiátricos.
- 3 February 2025
- Published by Brazilian Journals in Contribuciones A Las Ciencias Sociales
- Vol. 18 (2) , e15378
Open AccessO uso de Isotretinoína no tratamento da acne severa: avaliação do risco de depressão e outras alterações psiquiátricas
A acne severa é uma condição dermatológica que afeta negativamente a qualidade de vida dos pacientes, tanto fisicamente quanto emocionalmente. Quando tratamentos convencionais não são eficazes, a isotretinoína é uma alternativa frequentemente utilizada. Embora sua eficácia no tratamento da acne severa seja comprovada, seu uso tem sido associado a efeitos adversos na saúde mental, incluindo depressão, ansiedade e ideação suicida, levantando preocupações sobre a relação entre o medicamento e distúrbios psiquiátricos. O objetivo geral deste estudo é compreender os efeitos psicológicos do uso da isotretinoína no tratamento de acne severa, com foco no desenvolvimento de sintomas como depressão, ansiedade e ideação suicida. Os objetivos específicos incluem investigar o impacto da isotretinoína na saúde mental, explorar os mecanismos químicos relacionados a alterações de humor e sugerir estratégias de monitoramento e apoio emocional durante o tratamento. Este estudo consistE em uma revisão sistemática da literatura, conduzida por meio de bases de dados como PubMed, Scopus e Web of Science. Foram analisados artigos publicados entre 2010 e 2025 que investigaram a relação entre isotretinoína e transtornos psiquiátricos. A pesquisa seguiu as diretrizes PRISMA e incluiu estudos observacionais e ensaios clínicos randomizados. Os resultados indicam que, embora a isotretinoína seja altamente eficaz no tratamento da acne severa, seu uso pode estar relacionado ao agravamento de sintomas psiquiátricos, especialmente em indivíduos com vulnerabilidade emocional. Estudos mostram que alterações nos níveis de neurotransmissores como serotonina e dopamina podem ser um fator contribuidor. No entanto, a relação exata entre o medicamento e os distúrbios psiquiátricos ainda não é totalmente compreendida. O uso de isotretinoína, embora eficaz no tratamento da acne severa, deve ser acompanhado de cuidados psicológicos rigorosos. Pacientes com histórico de distúrbios emocionais devem ser monitorados de perto, e a administração do medicamento deve ser ajustada conforme a necessidade. A colaboração multidisciplinar é essencial para garantir que os benefícios dermatológicos do tratamento não sejam superados pelos riscos psiquiátricos.
- Open Access
- 1 October 2024
- Published by Research, Society and Development in Research, Society and Development
- Vol. 13 (10)
Estudo socioepidemiológico e impacto dos casos notificados de Leishmanioses em Teresina, Piauí, Brasil (2014-2022)
Objetivo: analisar os fatores temporais, geográficos e socioeconômicos que influenciam a incidência de leishmanioses em Teresina, entre 2014 e 2022. Metodologia: O estudo trata-se de uma avaliação realizada a partir de dados secundários, disponibilizados no Sistema de Informação de Agravos de Notificações (SINAN), por meio do site TABNET. As variáveis avaliadas foram classificadas em categorias geográficas, temporais, clínicas, demográficas, socioeconômicas e ambientais. Resultados: 1.246 casos de LVH e 300 casos de LTA foram notificados em Teresina na série histórica. A porcentagem de residentes de Teresina acometidos por LVH (máx. = 38,2%). A LTA apresentou maior porcentagem de residentes de Teresina acometidos (máx. = 67,1%). Os pacientes mais acometidos de LVH foi prevalente no sexo masculino (70,39%), pardas (88,12%), com faixa etária entre 20-39 anos (27,37%), com ensino fundamental completo (14,37%). Para a LTA, o perfil de acometidos foi para pacientes do sexo masculino (67%), raça parda (62%), com idade entre 40 a 59 anos (34,33%) com apenas ensino fundamental completo (22%). Dados ambientais mostram que a maior parte da população de Teresina possui abastecimento de água, assim como serviços de coleta de lixo, porém, a estrutura deficiente do saneamento básico atingiu 41,06% da população total. Conclusão: destaca-se a importância de fortalecer a vigilância e as estratégias de controle, além de integrar sistemas de informação de saúde para uma resposta mais eficaz.
- 1 October 2024
- Published by Research, Society and Development in Research, Society and Development
- Vol. 13 (10)
Open AccessEstudo socioepidemiológico e impacto dos casos notificados de Leishmanioses em Teresina, Piauí, Brasil (2014-2022)
Objetivo: analisar os fatores temporais, geográficos e socioeconômicos que influenciam a incidência de leishmanioses em Teresina, entre 2014 e 2022. Metodologia: O estudo trata-se de uma avaliação realizada a partir de dados secundários, disponibilizados no Sistema de Informação de Agravos de Notificações (SINAN), por meio do site TABNET. As variáveis avaliadas foram classificadas em categorias geográficas, temporais, clínicas, demográficas, socioeconômicas e ambientais. Resultados: 1.246 casos de LVH e 300 casos de LTA foram notificados em Teresina na série histórica. A porcentagem de residentes de Teresina acometidos por LVH (máx. = 38,2%). A LTA apresentou maior porcentagem de residentes de Teresina acometidos (máx. = 67,1%). Os pacientes mais acometidos de LVH foi prevalente no sexo masculino (70,39%), pardas (88,12%), com faixa etária entre 20-39 anos (27,37%), com ensino fundamental completo (14,37%). Para a LTA, o perfil de acometidos foi para pacientes do sexo masculino (67%), raça parda (62%), com idade entre 40 a 59 anos (34,33%) com apenas ensino fundamental completo (22%). Dados ambientais mostram que a maior parte da população de Teresina possui abastecimento de água, assim como serviços de coleta de lixo, porém, a estrutura deficiente do saneamento básico atingiu 41,06% da população total. Conclusão: destaca-se a importância de fortalecer a vigilância e as estratégias de controle, além de integrar sistemas de informação de saúde para uma resposta mais eficaz.
- 15 December 2023
- Published by Elsevier in Advanced Drug Delivery Reviews
- Vol. 205, 115156
Hurdles in translating science from lab to market in delivery systems for Cosmetics: An industrial perspective
- 15 December 2023
- Published by Elsevier in Advanced Drug Delivery Reviews
- Vol. 205, 115156
Hurdles in translating science from lab to market in delivery systems for Cosmetics: An industrial perspective
- 9 July 2021
- Published by Taylor & Francis in Biocatalysis and Biotransformation
- Vol. 41 (2) , 81-92
Correlation of the conformational structure and catalytic activity of the highly thermostable xylanase of Thermomyces lanuginosus PC7S1T
Thermomyces lanuginosus PC7S1T xylanase was purified after four chromatographic steps involving columns of ion exchange and molecular filtration. The purified xylanase revealed the molecular mass to be 21.3 kDa, high specificity for beechwood xylan and its main hydrolysis products were xylobiose and xylotriose. Xylanase exhibited increased activity at pH 6.5 and a temperature of 75 °C and was stable-over a wide range of pHs (100 hours) and temperatures (3 hours at 75 °C). Circular dichroism spectrum deconvolution showed a β-structure-rich secondary structure with a melting temperature of 73 °C. In addition, its secondary structure was preserved, even at extreme pHs and temperatures up to 70 °C in the presence of MnCl2 (1 mM), DTT (5 mM) and high concentrations of guanidine (6 M). On the other hand, changes in the tertiary structure of the enzyme, which was monitored using intrinsic and/or extrinsic fluorescence (ANS probe), in the presence of MnCl2, DTT and extreme values of pH may be related to variations in enzyme activity. Therefore, T. lanuginosus PC7S1T xylanase exhibited resistance to high temperatures, observed through its ability to remain active and demonstrate a high-degree of rigidity and resistance to denaturation; very extreme conditions were necessary in order to change the enzymes’ secondary and/or tertiary structures. Graphical Abstract
- 9 July 2021
- Published by Taylor & Francis in Biocatalysis and Biotransformation
- Vol. 41 (2) , 81-92
Correlation of the conformational structure and catalytic activity of the highly thermostable xylanase of Thermomyces lanuginosus PC7S1T
Thermomyces lanuginosus PC7S1T xylanase was purified after four chromatographic steps involving columns of ion exchange and molecular filtration. The purified xylanase revealed the molecular mass to be 21.3 kDa, high specificity for beechwood xylan and its main hydrolysis products were xylobiose and xylotriose. Xylanase exhibited increased activity at pH 6.5 and a temperature of 75 °C and was stable-over a wide range of pHs (100 hours) and temperatures (3 hours at 75 °C). Circular dichroism spectrum deconvolution showed a β-structure-rich secondary structure with a melting temperature of 73 °C. In addition, its secondary structure was preserved, even at extreme pHs and temperatures up to 70 °C in the presence of MnCl2 (1 mM), DTT (5 mM) and high concentrations of guanidine (6 M). On the other hand, changes in the tertiary structure of the enzyme, which was monitored using intrinsic and/or extrinsic fluorescence (ANS probe), in the presence of MnCl2, DTT and extreme values of pH may be related to variations in enzyme activity. Therefore, T. lanuginosus PC7S1T xylanase exhibited resistance to high temperatures, observed through its ability to remain active and demonstrate a high-degree of rigidity and resistance to denaturation; very extreme conditions were necessary in order to change the enzymes’ secondary and/or tertiary structures. Graphical Abstract
- Open Access
Biotechnological Potential of Araucaria angustifolia Pine Nuts Extract and the Cysteine Protease Inhibitor AaCI-2S
Protease inhibitors are involved in the regulation of endogenous cysteine proteases during seed development and play a defensive role because of their ability to inhibit exogenous proteases such as those present in the digestive tracts of insects. Araucaria angustifolia seeds, which can be used in human and animal feed, were investigated for their potential for the development of agricultural biotechnology and in the field of human health. In the pine nuts extract, which blocked the activities of cysteine proteases, it was detected potent insecticidal activity against termites (Nasutitermes corniger) belonging to the most abundant termite genus in tropical regions. The cysteine inhibitor (AaCI-2S) was purified by ion-exchange, size exclusion, and reversed-phase chromatography. Its functional and structural stability was confirmed by spectroscopic and circular dichroism studies, and by detection of inhibitory activity at different temperatures and pH values. Besides having activity on cysteine proteases from C. maculatus digestive tract, AaCI-2S inhibited papain, bromelain, ficin, and cathepsin L and impaired cell proliferation in gastric and prostate cancer cell lines. These properties qualify A. angustifolia seeds as a protein source with value properties of natural insecticide and to contain a protease inhibitor with the potential to be a bioactive molecule on different cancer cells.
Open AccessBiotechnological Potential of Araucaria angustifolia Pine Nuts Extract and the Cysteine Protease Inhibitor AaCI-2S
Protease inhibitors are involved in the regulation of endogenous cysteine proteases during seed development and play a defensive role because of their ability to inhibit exogenous proteases such as those present in the digestive tracts of insects. Araucaria angustifolia seeds, which can be used in human and animal feed, were investigated for their potential for the development of agricultural biotechnology and in the field of human health. In the pine nuts extract, which blocked the activities of cysteine proteases, it was detected potent insecticidal activity against termites (Nasutitermes corniger) belonging to the most abundant termite genus in tropical regions. The cysteine inhibitor (AaCI-2S) was purified by ion-exchange, size exclusion, and reversed-phase chromatography. Its functional and structural stability was confirmed by spectroscopic and circular dichroism studies, and by detection of inhibitory activity at different temperatures and pH values. Besides having activity on cysteine proteases from C. maculatus digestive tract, AaCI-2S inhibited papain, bromelain, ficin, and cathepsin L and impaired cell proliferation in gastric and prostate cancer cell lines. These properties qualify A. angustifolia seeds as a protein source with value properties of natural insecticide and to contain a protease inhibitor with the potential to be a bioactive molecule on different cancer cells.
- 1 November 2020
- Published by Elsevier in Carbohydrate Polymers
- Vol. 247, 116671
Identification of blood plasma proteins using heparin-coated magnetic chitosan particles
- 1 November 2020
- Published by Elsevier in Carbohydrate Polymers
- Vol. 247, 116671
Identification of blood plasma proteins using heparin-coated magnetic chitosan particles
- 15 September 2020
- Published by Royal Society of Chemistry (RSC) in Nanoscale
- Vol. 12 (37) , 19230-19240
Quantitative mechanistic model for ultrasmall nanoparticle–protein interactions
To date, extensive effort has been devoted toward the characterization of protein interactions with synthetic nanostructures. However, much remains to be understood, particularly concerning microscopic mechanisms of interactions. Here, we have conducted a detailed investigation of the kinetics of nanoparticle–protein complexation to gain deeper insights into the elementary steps and molecular events along the pathway for complex formation. Toward that end, the binding kinetics between p-mercaptobenzoic acid-coated ultrasmall gold nanoparticles (AuMBA) and fluorescently-labeled ubiquitin was investigated at millisecond time resolution using stopped-flow spectroscopy. It was found that both the association and dissociation kinetics consisted of multiple exponential phases, hence suggesting a complex, multi-step reaction mechanism. The results fit into a picture where complexation proceeds through the formation of a weakly-bound first-encounter complex with an apparent binding affinity (KD) of ∼9 μM. Encounter complex formation is followed by unimolecular tightening steps of partial desolvation/ion removal and conformational rearrangement, which, collectively, achieve an almost 100-fold increase in affinity of the final bound state (apparent KD ∼0.1 μM). The final state is found to be weakly stabilized, displaying an average lifetime in the range of seconds. Screening of the electrostatic forces at high ionic strength weakens the AuMBA–ubiquitin interactions by destabilizing the encounter complex, whereas the average lifetime of the final bound state remains largely unchanged. Overall, our rapid kinetics investigation has revealed novel quantitative insights into the molecular-level mechanisms of ultrasmall nanoparticle–protein interactions.
- 15 September 2020
- Published by Royal Society of Chemistry (RSC) in Nanoscale
- Vol. 12 (37) , 19230-19240
Quantitative mechanistic model for ultrasmall nanoparticle–protein interactions
To date, extensive effort has been devoted toward the characterization of protein interactions with synthetic nanostructures. However, much remains to be understood, particularly concerning microscopic mechanisms of interactions. Here, we have conducted a detailed investigation of the kinetics of nanoparticle–protein complexation to gain deeper insights into the elementary steps and molecular events along the pathway for complex formation. Toward that end, the binding kinetics between p-mercaptobenzoic acid-coated ultrasmall gold nanoparticles (AuMBA) and fluorescently-labeled ubiquitin was investigated at millisecond time resolution using stopped-flow spectroscopy. It was found that both the association and dissociation kinetics consisted of multiple exponential phases, hence suggesting a complex, multi-step reaction mechanism. The results fit into a picture where complexation proceeds through the formation of a weakly-bound first-encounter complex with an apparent binding affinity (KD) of ∼9 μM. Encounter complex formation is followed by unimolecular tightening steps of partial desolvation/ion removal and conformational rearrangement, which, collectively, achieve an almost 100-fold increase in affinity of the final bound state (apparent KD ∼0.1 μM). The final state is found to be weakly stabilized, displaying an average lifetime in the range of seconds. Screening of the electrostatic forces at high ionic strength weakens the AuMBA–ubiquitin interactions by destabilizing the encounter complex, whereas the average lifetime of the final bound state remains largely unchanged. Overall, our rapid kinetics investigation has revealed novel quantitative insights into the molecular-level mechanisms of ultrasmall nanoparticle–protein interactions.
- 26 June 2020
- Published by American Chemical Society (ACS) in Langmuir
- Vol. 36 (27) , 7991-8001
Regulation of Thrombin Activity with Ultrasmall Nanoparticles: Effects of Surface Chemistry
Nanomaterials displaying well-tailored sizes and surface chemistries can provide novel ways with which to modulate the structure and function of enzymes. Recently, we showed that gold nanoparticles (AuNPs) in the ultrasmall size regime could perform as allosteric effectors inducing partial inhibition of thrombin activity. We now find that the nature of the AuNP surface chemistry controls the interactions to the anion-binding exosites 1 and 2 on the surface of thrombin, the allosterically induced changes to the active-site conformation, and, by extension, the enzymatic activity. Ultrasmall AuNPs passivated with p-mercaptobenzoic acid ligands (AuMBA) and a peptide-based (Ac-ECYN) biomimetic coat (AuECYN) were utilized in our investigations. Remarkably, we found that while AuMBA binds to exosites 1 and 2, AuECYN interacts primarily with exosite 2. It was further established that AuMBA behaves as a “mild denaturant” of thrombin leading to catalytic dysfunction over time. Conversely, AuECYN resembles a proper allosteric effector leading to partial and reversible inhibition of the activity. Collectively, our findings reveal how the distinct binding modes of different AuNP types may uniquely influence thrombin structure and catalysis. The present study further contributes to our understanding of how synthetic nanomaterials could be exploited in the allosteric regulation of enzymes.
- 26 June 2020
- Published by American Chemical Society (ACS) in Langmuir
- Vol. 36 (27) , 7991-8001
Regulation of Thrombin Activity with Ultrasmall Nanoparticles: Effects of Surface Chemistry
Nanomaterials displaying well-tailored sizes and surface chemistries can provide novel ways with which to modulate the structure and function of enzymes. Recently, we showed that gold nanoparticles (AuNPs) in the ultrasmall size regime could perform as allosteric effectors inducing partial inhibition of thrombin activity. We now find that the nature of the AuNP surface chemistry controls the interactions to the anion-binding exosites 1 and 2 on the surface of thrombin, the allosterically induced changes to the active-site conformation, and, by extension, the enzymatic activity. Ultrasmall AuNPs passivated with p-mercaptobenzoic acid ligands (AuMBA) and a peptide-based (Ac-ECYN) biomimetic coat (AuECYN) were utilized in our investigations. Remarkably, we found that while AuMBA binds to exosites 1 and 2, AuECYN interacts primarily with exosite 2. It was further established that AuMBA behaves as a “mild denaturant” of thrombin leading to catalytic dysfunction over time. Conversely, AuECYN resembles a proper allosteric effector leading to partial and reversible inhibition of the activity. Collectively, our findings reveal how the distinct binding modes of different AuNP types may uniquely influence thrombin structure and catalysis. The present study further contributes to our understanding of how synthetic nanomaterials could be exploited in the allosteric regulation of enzymes.