par Gaertner, Hubert;Lebeau, Olivier;Borlat, Irène;Cerini, Fabrice;Dufour, Brigitte;Kuenzi, Gabriel;Melotti, Astrid;Fish, Richard J;Offord, Robin;Springael, Jean-Yves 
;Parmentier, Marc ;Hartley, Oliver
Référence Protein engineering, design & selection, 21, 2, page (65-72)
Publication Publié, 2008-02
;Parmentier, Marc ;Hartley, OliverRéférence Protein engineering, design & selection, 21, 2, page (65-72)
Publication Publié, 2008-02
Article révisé par les pairs
| Résumé : | The HIV coreceptor CCR5 is a validated target for both the prevention and therapy of HIV infection. PSC-RANTES, an N-terminally modified analogue of one of the natural chemokine ligands of CCR5 (RANTES/CCL5), is a potent inhibitor of HIV entry into target cells. Here, we set out to engineer the anti-HIV activity of PSC-RANTES into another natural CCR5 ligand (MIP-1beta/CCL4), by grafting into it the key N-terminal pharmacophore region from PSC-RANTES. We were able to identify MIP-1beta/CCL4 analogues that retain the receptor binding profile of MIP-1beta/CCL4, but acquire the very high anti-HIV potency and characteristic inhibitory mechanism of PSC-RANTES. Unexpectedly, we discovered that in addition to N-terminal structures from PSC-RANTES, the side chain of Lys33 is also necessary for full anti-HIV potency. |
