Peptides derived from N-terminal heptad repeat (NHR) of the HIV-1 gp41 are generally poor inhibitors of HIV-1 entry, because they tend to aggregate and do not form a trimeric coiled-coil. In this study, we have fused portions of gp41 NHR, e.g. N36 or N28, to the T4 fibritin trimerization domain, Foldon (Fd), thus constructing novel NHR trimers, designated N36Fd or N28Fd, which could be expressed in Escherichia coli cells. The purified N36Fd and N28Fd exhibited SDS-resistant trimeric coiled-coil conformation with improved ␣-helicity compared with the corresponding N-peptides. They could interact with a C-peptide (e.g. C34) to form stable six-helix bundle and possessed potent anti-HIV-1 activity against a broad spectrum of HIV-1 strains. N28Fd was effective against T20-resistant HIV-1 variants and more resistant to proteinase K compared with T20 (enfuvirtide), a C-peptide-based HIV fusion inhibitor. Therefore, N28Fd trimer has great potentials for further development as an affordable therapeutic or microbicide for treatment and prevention of HIV-1 infection.
[1] We analyzed observation data collected by the Instrument for the Detection of Particles (IDP) on board the DEMETER satellite during a period of 17 months in 2007 and 2008. In the meantime, the VLF transmitter located at North West Cape (NWC) ground station was shut down during 7 months and working for a total of 10 months. By an (on-off) method, our analysis for the first time revealed in detail the transient properties of the space electron precipitation belt which is induced by the man-made VLF wave emitted from NWC. We mapped the electron flux distribution and figured out the space regions that the NWC belt covered. The NWC electron spectrograms have been investigated in a wide range of the McIlwain parameter L (1.1-3.0). Furthermore, we obtained the averaged energy spectra of the NWC electrons within the drift loss cone and compared their characteristics during daytime and nighttime. Our results confirm the previous studies of the enhancement of NWC electrons, the wisp structure, and the day/night difference of the electron flux. In addition, more detailed information is provided. We provide not only evidence of a momentary flux enhancement up to 3 orders of magnitude but also a flux reduction at higher L shells with a maximum up to 60% of the original value. For the first time, the energy spectra of NWC electrons covering the entire IDP energy band are presented for both nighttime and daytime and are quantitatively compared. At the end, our results are discussed, and their agreement with the theory of wave-particle interactions is checked.
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