Self-association of an amphipathic helix peptide inhibitor of HIV-1 integrase assessed by electro spray ionization mass spectrometry in trifluoroethanol/water mixtures
S. Fermandjian et al., Self-association of an amphipathic helix peptide inhibitor of HIV-1 integrase assessed by electro spray ionization mass spectrometry in trifluoroethanol/water mixtures, RAP C MASS, 15(5), 2001, pp. 320-324
Establishing the auto-associative properties of a molecule in solution can
be important for determination of its structure and function. EAA26 (VESMNE
ELKKIIAQVRAQAEHLKTAY) has been designed to inhibit HIV-1 integrase via form
ation of a stable coiled-coil structure with a nearly homologous segment in
the enzyme. The latter catalyzes the permanent incorporation of a DNA copy
of the retrovirus genome into host cell DNA, and is thus essential to the
life of the retrovirus. This makes integrase an obvious drug target in the
therapy of AIDS. The present work has demonstrated, using electrospray ioni
zation mass spectrometry (ESI-MS), that EAA26 is monomeric in pure water, a
nd tetrameric and dimeric at respectively low and medium concentrations of
2,2,2-trifluoroethanol (TFE), and again monomeric at higher TFE concentrati
ons. Thus, the apolar solvent TFE may contribute to either stabilization or
disruption of the intermolecular hydrophobic contacts depending on its con
centration in aqueous solution. Previous NMR and ultracentifugation results
are thus confirmed, indicating the reliability of ESI-MS for defining the
self-association state of biologically relevant peptides in both water and
organic-water solutions. Copyright (C) 2001 John Wiley & Sons, Ltd.