Conformational studies of RGDechi peptide by natural-abundance NMR spectroscopy(24 visite) Farina B, Del Gatto A, Comegna D, Di Gaetano S, Capasso D, Isernia C, Saviano M, Fattorusso R, Zaccaro L, Russo L
Impact factor: 1.807, Impact factor a 5 anni: 1.872
Url: Non disponibile.
Parole chiave: Integrin, Natural-Abundance Nmr, Recognition Mechanism, Structure-Activity Relationship
Affiliazioni:
*** IBB - CNR *** Institute of Biostructures and Bioimaging, CNR, Naples, Italy., Interdepartmental Center of Bioactive Peptide, University of Naples Federico II, Naples, Italy., Department of Pharmacy, University of Naples Federico II, Naples, Italy., Department of Environmental, Biological and Pharmaceutical Science and Technology, University of Campania Luigi Vanvitelli, Caserta, Italy., Institute of Crystallography, CNR, Bari, Italy.,
Riferimenti:
Non disponibile.
Integrins are heterodimeric cell-surface proteins that play important roles during developmental and pathological processes. Diverse human pathologies involve integrin adhesion including thrombotic diseases, inflammation, tumour progression, fibrosis, and infectious diseases. Although in the past decade, novel integrin-inhibitor drugs have been developed for integrin-based medical applications, the structural determinants modulating integrin-ligands recognition mechanisms are still poorly understood, reducing the number of integrin subtype exclusive antagonists. In this scenario, we have very recently showed, by means of chemical and biological assays, that a chimeric peptide (named RGDechi), containing a cyclic RGD motif linked to an echistatin C-terminal fragment, is able to interact with the components of integrin family with variable affinities, the highest for alphav beta3. Here, in order to understand the mechanistic details driving the molecular recognition mechanism of alphav beta3 by RGDechi, we have performed a detailed structural and dynamics characterization of the free peptide by natural abundance nuclear magnetic resonance (NMR) spectroscopy. Our data indicate that RGDechi presents in solution an heterogeneous conformational ensemble characterized by a more constrained and rigid pentacyclic ring and a largely unstructured acyclic region. Moreover, we propose that the molecular recognition of alphav beta3 integrin by RGDechi occurs by a combination of conformational selection and induced fit mechanisms. Finally, our study indicates that a detailed NMR characterization, by means of natural abundance (15) N and (13) C, of a mostly unstructured bioactive peptide may provide the molecular basis to get essential structural insights into the binding mechanism to the biological partner.
129 Records (123 escludendo Abstract e Conferenze). Impact factor totale: 490.528 (467.817 escludendo Abstract e Conferenze). Impact factor a 5 anni totale: 486.666 (461.673 escludendo Abstract e Conferenze).
ibb.cnr.it
