ABSTRACT: Assembly of the mature human immunodeficiency virus type 1 capsid involves the oligomerization of the capsid protein, CA. The C-terminal domain of CA, CTD, participates both in the formation of CA hexamers and in the joining of hexamers through homodimerization. Intact CA and the isolated CTD are able to homodimerize in solution with similar affinity (dissociation constant in the order of 10 microM); CTD homodimerization involves mainly an alpha-helical region. In this work, we show that first-generation gallic acid-triethylene glycol (GATG) dendrimers bind to CTD. The binding region is mainly formed by residues involved in the homodimerization interface of CTD. The dissociation constant of the dendrimer-CTD complexes is in the range of micromolar, as shown by ITC. Further, the affinity for CTD of some of the dendrimers is similar to that of synthetic peptides capable of binding to the dimerization region, and it is also similar to the homodimerization affinity of both CTD and CA. Moreover, one of the dendrimers, with a relatively large hydrophobic moiety at the dendritic branching (a benzoate), was able to hamper the assembly in vitro of the human immunodeficiency virus capsid. These results open the possibility of considering dendrimers as lead compounds for the development of antihuman immunodeficiency virus drugs targeting capsid assembly.
Biomacromolecules 08/2010; 11(8):2069-78. · 5.48 Impact Factor