INVESTIGADORES
HOLLMANN Axel
congresos y reuniones científicas
Título:
Improvement of the HIV fusion inhibitor C34 activity by membrane anchoring and enhanced exposure.
Autor/es:
AUGUSTO, MT; HOLLMANN A; CASTANHO MA; PESSI A; SANTOS NC
Lugar:
Lisboa
Reunión:
Congreso; 9th European Biophysics Congress; 2013
Institución organizadora:
EBSA
Resumen:
It was recently demonstrated that the
combination of cholesterol-tagging, by using a PEG moiety as spacer and
dimerization of the C34 peptide sequence, resulted in an increase of the
antiviral potency and in an extension of the in vivo half-life of these HIV fusion inhibitors, named HIVP3
(C34-PEG4-cholesterol) and HIVP4 ([C34-PEG4]2-cholesterol).
The aim of the present work was to evaluate the interaction of these molecules with
membrane model systems and human blood cells. Membrane partition, dipole
potential and pressure assays indicate that HIVP3 and HIVP4 interact
preferentially with cholesterol-rich liquid ordered membranes mimicking
biological membranes microdomains, known as lipid rafts. Interaction of
peptides with human erythrocytes and peripheral blood mononuclear cells (PBMC) showed
that HIVP3 and HIVP4 are able to interact with the membrane of both blood cells
in the same extension as another C34 derivate, C34-cholesterol. However, the
pocket binding domain (PBD) of both new C34 derivates seems to be more exposed
to the aqueous environment than on C34-cholesterol. All this data indicate that
the synergic effect between a membranotropic behavior and an enhanced exposure
of PBD of the inhibitors result in a more efficient blocking of HIV entry.