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G1_G2_NAINHIBIT

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Design synthesis and evaluation of potential group 1 and group 2 neuraminidase...

Design synthesis and evaluation of potential group 1 and group 2 neuraminidase inhibitors Influenza neuraminidase (NA) is the enzyme that releases influenza virions from the infected cells, cleaving the sialic acid receptor on host cells. It has been recently demonstrated that influenza A has neuraminidase subtypes tha... ver más

31/12/2016

UMIL

228K€

Presupuesto del proyecto: 228K€

Líder del proyecto

UNIVERSITA DEGLI STUDI DI MILANO No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2016-12-31 No tenemos la información de la convocatoria

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1 Participantes

UMIL

0.00€ | Lider

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Líder del proyecto

UNIVERSITA DEGLI STUDI DI MILANO No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 228K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Influenza neuraminidase (NA) is the enzyme that releases influenza virions from the infected cells, cleaving the sialic acid receptor on host cells. It has been recently demonstrated that influenza A has neuraminidase subtypes that belong to two distinct subgroups. The crystal structures of the three subtypes N1, N4 and N8 (group-1 enzymes) were found to be virtually identical in the shapes of their active sites. However they were found to be different when compared to N2 and N9 subtypes (group-2 enzymes). In the case of N1, N4 and N8 subtypes, a loop of amino acids which includes the active site catalytic residue Asp 151, was found to adopt an unusual open conformation compared to the N2 and N9 subtypes in which loop-150 was of a closed conformation. The observation of different active site conformations between certain subtypes of group-1 and group-2 enzymes suggests that these two groups are not only genetically distinct but are also structurally distinct. The main objective of our project is to develop new specific neuraminidase inhibitors with two distinctive important features: 1) a novel general scaffold which provides the correct ring distortion required to mimic both group-1 and group-2 neuraminidase transition-state; 2) further additional groups of suitable shape and size that extend the general structure and fill the cavity-150, with the aim of generate group-1 specific inhibitors. The objectives of the project will be achieved through the employment of multidisciplinary competences, in which the host institutions have enormous experience: design of carbohydrate mimics as inhibitors, libraries synthesis, virus like particles STD-NMR spectroscopy, biological evaluation and molecular modelling.This fellowship will ensure the opportunity for the applicant to be exposed to an international and interdisciplinary context, working on a timely scientific project resulting from the collaboration of two internationally recognized research leaders in glycoscience.

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