Engineering a CD4 mimetic inhibiting the binding of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein gp120 to human lymphocyte CD4 by the transfer of a CD4 functional site to a small natural scaffold |
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Authors: | Eugenia Drakopoulou Jean Vizzavona Claudio Vita |
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Affiliation: | (1) CEA, Département d'Ingénierie et d'Etudes des Protéines, C.E. Saclay, F-91190 Gif-sur-Yvette, France |
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Abstract: | The solvent-exposed CDR2-like region of human CD4 was transferred to the structural scaffold of scorpion charybdotoxin, as a means to reproduce that site in a native-like conformation. The chimeric mini-protein (33 amino acids long), obtained by solid-phase synthesis, is able to specifically prevent the interaction of HIV-1 gp120 with CD4. This CD4 mimetic may represent a valuable tool in the study of the HIV–cell interactions and as a lead in the development of antiviral drugs. |
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Keywords: | active site transfer chimeric mini-protein drug lead HIV inhibitor |
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