Data di Pubblicazione:
2008
Citazione:
Binding of RGD-peptide mimics to intact human platelets : an NMR study / D. Potenza, L. Belvisi, F. Vasile, M. Civera, L. Manzoni. ((Intervento presentato al convegno Meeting "Magnetic resonance in the life sciences: What's
New" tenutosi a Montecatini, Italia nel 2008.
Abstract:
The interactions of small peptides with biological membranes is central to a number of biological
processes. In contrast to soluble proteins there is comparatively little information available about ligandreceptor
interactions that occur at membrane surfaces. The biophysical environment of a membrane is
considerably different from the isotropic extracellular medium. It is therefore desirable to investigate
membrane proteins and their binding specificity directly in living cells. The integrin aIIbb3 is the most
abundant platelet cell surface glycoprotein and plays a key role in adhesion of platelet to protein-coated
surfaces and platelet/platelet aggregation. Therefore, aIIbb3 receptor is an excellent target for drug design
and delivery. The ligands are cyclic pentapeptide mimics incorporating stereoisomeric 5,6- and 5,7-fused
bicyclic lactams and the tripeptide sequence Arg-Gly-Asp (RGD)[1], a common amino acid motif found in
a number of adhesive proteins.
In order to study these binding processes at molecular level, we used trNOE experiments directly on
whole human platelets.[2] Conformational properties of the free and bound mimics are investigated by
computational and NMR studies.
Utilizing structural information by NMR tr-NOE experiments and docking studies, we have discovered a
new higher affinity aIIbb3 ligand, which is able to inhibit the adhesion of platelets.
Tipologia IRIS:
14 - Intervento a convegno non pubblicato
Keywords:
NMR ; Human platelet ; ligand-protein interaction
Elenco autori:
D. Potenza, L. Belvisi, F. Vasile, M. Civera, L. Manzoni
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