Angelo Santoro, Michela Buonocore, Mohammad Firoznezhad, Manuela Grimaldi, Anna Maria D'Ursi
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引用次数: 0
Abstract
Feline immunodeficiency virus (FIV) shares structural similarities with human immunodeficiency virus (HIV): the surface glycoprotein gp36 corresponds to the HIV gp41, which drives virus-host cell interactions and is targeted by the peptide entry inhibitor enfuvirtide. Following a similar drug design strategy for the development of an anti-FIV therapy, the present study investigates 627-646gp36 NHR, a peptide sequence derived from a region of gp36 that was previously found to interfere with the antiviral activity of the peptide C8, which instead derives from the gp36 MPER. CD, NMR, and MD simulations were employed to probe the conformational characteristics of 627-646gp36 NHR in the membrane-mimicking environment of SDS micelles. Our data show that 627-646gp36 NHR is characterized by three dynamic helix structures. MD simulations involving 627-646gp36 NHR, C8, and a larger protein, including the CHR and MPER regions, suggest that the interaction of C8 with the MPER region, the origin of the antiviral activity of C8, is disfavored in the presence of 627-646gp36 NHR in the simulation. This evidence can be useful for interpreting the molecular mechanism that leads to interference with the activity of C8, providing information on the folding/unfolding mechanism of the viral glycoprotein to design new strategies to inhibit viral entry.
期刊介绍:
The official Journal of the European Peptide Society EPS
The Journal of Peptide Science is a cooperative venture of John Wiley & Sons, Ltd and the European Peptide Society, undertaken for the advancement of international peptide science by the publication of original research results and reviews. The Journal of Peptide Science publishes three types of articles: Research Articles, Rapid Communications and Reviews.
The scope of the Journal embraces the whole range of peptide chemistry and biology: the isolation, characterisation, synthesis properties (chemical, physical, conformational, pharmacological, endocrine and immunological) and applications of natural peptides; studies of their analogues, including peptidomimetics; peptide antibiotics and other peptide-derived complex natural products; peptide and peptide-related drug design and development; peptide materials and nanomaterials science; combinatorial peptide research; the chemical synthesis of proteins; and methodological advances in all these areas. The spectrum of interests is well illustrated by the published proceedings of the regular international Symposia of the European, American, Japanese, Australian, Chinese and Indian Peptide Societies.