Self-selection of a multivalent nanosystem for carbohydrate recognition

Información del proyecto

NANOCARB

Identificador del acuerdo de subvención: 657486

DOI

10.3030/657486

Proyecto cerrado

Fecha de la firma de la CE 17 Marzo 2015

Fecha de inicio 15 Abril 2015

Fecha de finalización 14 Abril 2017

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 180 277,20

Aportación de la UE

€ 180 277,20

Coordinado por

UNIVERSITA DEGLI STUDI DI PADOVA
Italy

Periodic Reporting for period 1 - NANOCARB (Self-selection of a multivalent nanosystem for carbohydrate recognition)

Período documentado: 2015-04-15 hasta 2017-04-14

Resumen del contexto y de los objetivos generales del proyecto

Carbohydrates are one of the most fundamental molecules in living systems. The functioning of cellular system like signal transduction, cell-to-cell communication, cell adhesion, and even cancer metastasis are controlled by carbohydrates. It is therefore necessary to find proper ways of recognizing carbohydrates not only to understand cellular phenomena but also because carbohydrates are imperative biomarkers as well as therapeutics for different pathologies, including diabetes, cardiovascular diseases, cancers etc. Also, the specific binding of different proteins with cell surface carbohydrate receptors is the most decisive event in governing cell functioning. In this context, the NANOCARB project has the objective to build up an original method for the development of an innovative class of carbohydrate receptors using dynamic combinatorial chemistry (DCC) on the surface of a gold nanoparticle. Dynamic combinatorial chemistry (DCC) relies on the spontaneous shift in the composition of a library of interconverting molecules upon the addition of a target. This eliminates the problem of rational design as the selection is performed by the molecules themselves. In the past decade, DCC has emerged as a powerful tool for the development of receptors, catalysts, and materials. The combination of monolayer protected gold nanoparticles (AuNPs) and DCC might add a new dimension for the development of protein-like receptors or sensors for carbohydrates due to several attractive features i) multivalency, ii) high stability of the nanosystems in physiologically relevant conditions, iii) intrinsic photochemical properties originating from the gold core.
A positive outcome of the project is a deeper understanding of how multivalent interactions can be used to regulate (bio)chemical processes. It has been shown, using gold nanoparticles and other surfactant-based multivalent systems, that multivalency can be exploited to create structures for sensing and catalysis under physiologically relevant conditions. DCC has been used to develop sensing systems able to detect toxic heavy metal ions at nanomolar concentrations in water. The development of these concepts took longer than foreseen and two years of research has been insufficient to implement this system for carbohydrate recognition. Promising initial results have been obtained which validate the chosen approach.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

The work performed in this project has covered several aspects related to the main scope, which is the development of dynamic combinatorial chemistry on multivalent nanoparticles as tool to develop carbohydrate recognition.

Multivalency (publications 1 - 3). Two systems were studied: monolayer protected gold nanoparticles and surfactant-based aggregates. It was found that the presence of multiple negatively charged groups in the analyte were required to establish sufficiently strong interactions to permit binding at low micromolar concentrations in aqueous buffer. Importantly, this discovery led to the unexpected insight that this interaction can be used to create supramolecular systems with a well-defined lifetime by adding enzymes able to cleave negatively charged groups from the substrate (which included phosphorylated sugars).

Dynamic combinatorial chemistry (publication 4). The concept of DCC on gold nanoparticles was validated using metal ions as analytes, rather than carbohydrates, because of the higher strength of interaction with the recognition modules. These results showed important features such as the ability to tune the assay selectivity, sensitivity and dynamic detection range.

Carbohydrate recognition. Finally, a significant effort has been made to exploit these insights for developing a chemosensing systems for carbohydrate detection. It has been found that the NP surface can discriminate between three monophosphate analogues of glucose. The binding affinity towards the NP surface was as follows: β-glucose-1-phosphate> glucose-6-phosphate > α-glucose-1-phosphate. Also, the NP surface was able to differentiate between glucose-6-phosphate and mannose-6-phosphate where glucose-6-phosphate showed higher affinity and was distinguishable even at 200 μM. Finally, preliminary studies revealed that the presence of an additional peptide on the monolayer surface affects the selectivity of the carbohydrate recognition process.

Publications
[1] S. Maiti, I. Fortunati, C. Ferrante, P. Scrimin and L.J. Prins. Nat. Chem. 2016, 8, 725-731
[2] J. L.-Y. Chen, S. Maiti, I. Fortunati, C. Ferrante and L.J. Prins, Chem. Eur. J. 2017, 10.1002/chem.201701533
[3] F. della Sala, S. Neri, S. Maiti, J. L.-Y. Chen, L.J. Prins, Curr.Opin. Biotech. 2017, 10.1016/j.copbio.2016.10.014
[4] S. Maiti, L. J. Prins, Tetrahedron, 2017, 10.1016/j.tet.2017.05.028

Conferences
1. Subhabrata Maiti “Dissipative self-assembly of vesicular nanoreactors fueled by ATP”. “Gordon Research Seminar on Bioinspired Materials” held at Les Diabetreles Conference Centre, Switzerland, June 4-5, 2016.
2. Subhabrata Maiti, “Dissipative self-assembly of vesicular nanoreactors fueled by ATP”. “Gordon Research Conference on Bioinspired Materials” held at Les Diabetreles Conference Centre, Switzerland, June 5-10, 2016.
3. Subhabrata Maiti, “Dynamic combinatorial chemistry on a monolayer protected gold nanoparticle” “International Symposium on Macrocyclic and Supramolecular Chemistry 2015” held at Strasbourg, France, June 28-July 2, 2016.
4. Participated in the “European-Winter School on Physical Organic Chemistry (E-WiSPOC)” organized by University of Padova and of the Organic Division of the Italian Chemical Society, Bressanone, Italy on January 31-February 5, 2016.
5. Participated in the program jointly organized by the university and the European Research Council “European Charter for Researchers and the Code of Conduct for the Recruitment of Researchers (C&C)”, February 29, 2016 held at University of Padova.

Invited seminars
1. “Transient and Adaptive Organization in Nanosystems” as institute seminar in “IISER Pune”, Pune, India, January 5, 2017.
2. “Transient and Adaptive Organization in Nanosystems” as institute seminar in “Jawaharlal Nehru Center for Advanced Scientific Research (JNCASR)”, Bangalore, India, January 12, 2017.

Public outreach

Department of Chemical Sciences' chemistry fair (24th September, 2016) (It’s not Magic, it’s Chemistry)
Seminar: ‘My Chemical Life in Padova: From a Postdoc to Marie-Curie Researcher’; 30th September, 2016, Palazzo bo, Padova.
Video : https://www.youtube.com/watch?v=bePWMRMsPSU.
Also featured in Le Scienze (Italian Edition of Scientific American); Online link: http://www.lescienze.it/lanci/2016/05/04/news/universita_degli_studi_di_padova_ecco_come_le_molecole_si_organizzano_in_cellule-3077949/

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

1. Insight in the importance of multivalent interactions in regulating molecular recognition processes
2. Exploitation of multivalent interactions for the transient activation of chemical processes
3. Modular sensing assay for the detection of toxic heavy metal ions at nanomolar concentrations in water
4. Sensing assay with tunable sensitivity, selectivity and dynamic detection range
5. Carbohydrate binding by monolayer protected gold nanoparticles
6. Selective recognition of carbohydrates on multivalent nanoparticles

These results provide new perspectives for the development of diagnostic assays and preliminary results indicate a novel strategy for detecting carbohydrates.

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