Molecular engineering of Rantes peptide mimetics with potent anti-HIV-1 activity (Articolo in rivista)

Type

• Articolo in rivista (Classe)
• Prodotto della ricerca (Classe)

Label

• Molecular engineering of Rantes peptide mimetics with potent anti-HIV-1 activity (Articolo in rivista) (literal)

Anno

• 2011-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

• 10.1096/fj.10-167627 (literal)

Alternative label

• Lusso P., Vangelista L., Cimbro R., Secchi M., Sironi F., Longhi R., Faiella M., Maglio O., Pavone V. (2011)
  Molecular engineering of Rantes peptide mimetics with potent anti-HIV-1 activity
  in The FASEB journal
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Lusso P., Vangelista L., Cimbro R., Secchi M., Sironi F., Longhi R., Faiella M., Maglio O., Pavone V. (literal)

Pagina inizio

• 1230 (literal)

Pagina fine

• 1243 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 25 (literal)

Rivista

• ?The ?FASEB journal (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali

• 14 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

• 4 (literal)

Note

• ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Unit of Human Virology, Department of Biological and Technological Research (DIBIT), San Raffaele Scientific Institute, Milan, Italy. Istituto di Biostrutture e Biommagini, CNR, NAPOLI, Italty (literal)

Titolo

• Molecular engineering of Rantes peptide mimetics with potent anti-HIV-1 activity (literal)

Abstract

• The chemokine receptor CCR5 is utilized as a critical coreceptor by most primary HIV-1 strains. While the lack of structural information on CCR5 has hampered the rational design of specific inhibitors, mimetics of the chemokines that naturally bind CCR5 can be molecularly engineered. We used a structure-guided approach to design peptide mimetics of the N-loop and ?1-strand regions of regulated on activation normal T-cell-expressed and secreted (RANTES)/CCL5, which contain the primary molecular determinants of HIV-1 blockade. Rational modifications were sequentially introduced into the N-loop/?1-strand sequence, leading to the generation of mimetics with potent activity against a broad spectrum of CCR5-specific HIV-1 isolates (IC(50) range: 104-640 nM) but lacking activity against CXCR4-specific HIV-1 isolates. Functional enhancement was initially achieved with the stabilization of the N loop in the ?-extended conformation adopted in full-length RANTES, as confirmed by nuclear magnetic resonance (NMR) analysis. However, the most dramatic increase in antiviral potency resulted from the engraftment of an in silico-optimized linker segment designed using de novo structure-prediction algorithms to stabilize the C-terminal ?-helix and experimentally validated by NMR. Our mimetics exerted CCR5-antagonistic effects, demonstrating that the antiviral and proinflammatory functions of RANTES can be uncoupled. RANTES peptide mimetics provide new leads for the development of safe and effective HIV-1 entry inhibitors. (literal)

Prodotto di

• simulazioni molecolari di sistemi biologici (INT.P02.001.001) (Modulo)
• Le proprietà magnetiche di radicali di interesse biologico ed ambientale: un approccio multiscala (PM.P07.005.003) (Modulo)
• Institute of biostructure and bioimaging (IBB) (Istituto)
• Istituto di chimica del riconoscimento molecolare (ICRM) (Istituto)

Autore CNR

• ORNELLA MAGLIO (Unità di personale interno)
• RENATO LONGHI (Unità di personale interno)

Incoming links:

Autore CNR di

• RENATO LONGHI (Unità di personale interno)
• ORNELLA MAGLIO (Unità di personale interno)

Prodotto

• Istituto di chimica del riconoscimento molecolare (ICRM) (Istituto)
• Institute of biostructure and bioimaging (IBB) (Istituto)
• simulazioni molecolari di sistemi biologici (INT.P02.001.001) (Modulo)
• Le proprietà magnetiche di radicali di interesse biologico ed ambientale: un approccio multiscala (PM.P07.005.003) (Modulo)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• ?The ?FASEB journal (Rivista)