Designing inhibitors against the capsid protein of HIV-1

NEIRA, JOSE L.; DOMENECH, R.; BOCANEGRA, R.; ABIÁN, OLGA; CORREA, J.; SOUSA-HERVÉS, A.; BUENO, MARTA; VELÁZQUEZ-CAMPOY, ADRIÁN; CAVASOTTO, CLAUDIO N.; RIGUERA, R.; SANCHO, JAVIER; FERNÁNDEZ, E.; MATEU, MAURICIO G.

Zaragoza

Conferencia; V National Conference BIFI 2011; 2011

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 ?Ñ-helical region. In this communication we show a ten-years-long project involving an almost exhaustive knowledge of the folding and energetics of the CTD to the design of molecules (peptides and dendrimers) able to bind the protein, and interfere with the oligomerization of the whole protein.