1,721,120 research outputs found
Binding of RGD-peptide Mimics to intact Human Platelets: an NMR Study
No full textThe interactions of small peptides with biological membranes is central to a number of biological processes. Interference with these recognition events could be used to modulate or alter signal transmission or to prevent the onset of deseaes. 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. We are investigating these problems using as model the integrin IIb3 which is the most abundant platelet cell surface glycoprotein. This integrin plays a key role in adhesion of platelet to protein-coated surfaces and in platelet/platelet aggregation. Therefore, IIb3 receptor is an excellent target for drug design.
New cyclic pentapeptide mimics (1) were designed incorporating the tripeptide sequence Arg-Gly-Asp (RGD)[1], a common amino acid motif found in a number of adhesive proteins.
In order to study the binding processes between the platelet IIb3 integrin and the RGD ligands, at molecular level, we used transfer-NOE and STD (Saturated Transfer Difference) experiments directly on whole human platelets.[2]
NMR studies were performed to investigate the conformation of the peptidomimetics, first in solution and then upon binding to platelets by transferred nuclear Overhauser effect (TR-NOE) measurements. STD experiments were also performed in order to define the portions of the ligands which are in closest contact with the protein. Analysis of the NMR data allowed to correlate the biological results and to derive workable models of the ligand:protein complexes.
Utilizing structural information by NMR experiments and docking studies, we have discovered a new high affinity IIb3 ligand, which is able to inhibit the platelet aggregation and the adhesion of fibrinogen to platelet
Binding of rgd-peptide mimics to intact human platelets investigated by transferred-noesy experiments
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Transferred-NOE NMR Experiments on Intact Human Platelets: Receptor-Bound Conformation of RGD-Peptide Mimics.
No full textThe aim of this work is to show that transferred-NOE provides useful and detailed information on membrane-bound receptor-ligand interactions in living cells. Here, we study the interaction between intact human platelets and some ligands containing the RGD sequence. Conformational properties of the free and bound pentapeptides are reported. This journal i
A 13C and 1H n.m.r. Study of Diastereomeric alpha-Methylidene-beta-hydroxy-gamma-alkoxyesters
No full textThe 13C and 1H NMR spectra of α-methylidene-β-hydroxy-γ-alkoxy-pentanoates and -decanoates are presented. These data are consistent with a preferred conformation in which an intramolecular hydrogen bond is present. Very characteristic steric shifts in the 13C and 1H NMR spectra provide an efficient tool for the configurational assignment for this class of compounds
Conformational behaviour of small cyclic and linear peptidomimetics containing a 5,6-fused bicyclic lactam
No full textTRANSFERRED-NOESY NMR EXPERIMENTS ON LIVING CELLS : RGD DERIVATIVES BIND PLATELET INTEGRIN aIIbb3
No full textAnalisi NMR delle interazioni tra peptidomimetici e proteine di membrana in cellule intatte
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