2 research outputs found
Negatively Charged Glyconanoparticles Modulate and Stabilize the Secondary Structures of a gp120 V3 Loop Peptide: Toward Fully Synthetic HIV Vaccine Candidates
The
third variable region (V3 peptide) of the HIV-1 gp120 is a
major immunogenic domain of HIV-1. Controlling the formation of the
immunologically active conformation is a crucial step to the rational
design of fully synthetic candidate vaccines. Herein, we present the
modulation and stabilization of either the Ī±-helix or Ī²-strand
conformation of the V3 peptide by conjugation to negatively charged
gold glyconanoparticles (GNPs). The formation of the secondary structure
can be triggered by the variation of the buffer concentration and/or
pH as indicated by circular dichoism. The peptide on the GNPs shows
increased stability toward peptidase degradation as compared to the
free peptide. Moreover, only the V3Ī²-GNPs bind to the anti-V3
human broadly neutralizing mAb 447-52D as demonstrated by surface
plasmon resonance (SPR). The strong binding of V3Ī²-GNPs to the
447-52D mAb was the starting point to address its study as immunogen.
V3Ī²-GNPs elicit antibodies in rabbits that recognize a recombinant
gp120 and the serum displayed low but consistent neutralizing activity.
These results open up the way for the design of new fully synthetic
HIV vaccine candidates
Isolation, Structural Modification, and HIV Inhibition of Pentacyclic Lupane-Type Triterpenoids from <i>Cassine xylocarpa</i> and <i>Maytenus cuzcoina</i>
As a part of our investigation into
new anti-HIV agents, we report
herein the isolation, structure elucidation, and biological activity
of six new (<b>1</b>ā<b>6</b>) and 20 known (<b>7</b>ā<b>26</b>) pentacyclic lupane-type triterpenoids
from the stem of <i>Cassine xylocarpa</i> and root bark
of <i>Maytenus cuzcoina</i>. Their stereostructures were
elucidated on the basis of spectroscopic and spectrometric methods,
including 1D and 2D NMR techniques. To gain a more complete understanding
of the structural requirements for anti-HIV activity, derivatives <b>27</b>ā<b>48</b> were prepared by chemical modification
of the main secondary metabolites. Sixteen compounds from this series
displayed inhibitory effects of human immunodeficiency virus type
1 replication with IC<sub>50</sub> values in the micromolar range,
highlighting compounds <b>12</b>, <b>38</b>, and <b>42</b> (IC<sub>50</sub> 4.08, 4.18, and 1.70 Ī¼M, respectively)
as the most promising anti-HIV agents