3 research outputs found
Omega‑3 Fatty Acids Regulate the Interaction of the Alzheimer’s Aβ(25–35) Peptide with Lipid Membranes
Polyunsaturated
omega-3 fatty acids are increasingly proposed as
dietary supplements able to reduce the risk of development or progression
of the Alzheimer’s disease (AD). To date, the molecular mechanism
through which these lipids act has not been yet univocally identified.
In this work, we investigate whether omega-3 fatty acids could interfere
with the fate of the Alzheimer-related amyloid peptide by tuning the
microstructural and dynamical properties of the neuronal membrane.
To this aim, the influence of the omega-3 lipid, 1,2-didocosahexaenoyl-<i>sn</i>-glycero-3-phosphocholine [22:6Â(<i><i>cis</i></i>)ÂPC] on the biophysical properties of lipid bilayers, and
on their interaction with the amyloid peptide fragment Aβ(25–35)
has been investigated by Electron Spin Resonance (ESR), using spin-labeled
phospholipids. The results show that the peptide selectively interacts
with bilayers enriched in cholesterol (Chol) and sphingomyelin (SM).
[22:6Â(<i><i>cis</i></i>)ÂPC] enhances the Aβ(25–35)/membrane
interaction, favoring a deeper internalization of the peptide among
the lipid acyl chains and, consequently, hindering its pathogenic
self-aggregation
Structural Evidence of <i>N</i>6‑Isopentenyladenosine As a New Ligand of Farnesyl Pyrophosphate Synthase
<i>N</i>6-isopentenyladenosine (i6A), a modified nucleoside
belonging to the cytokinin family, has shown in humans many biological
actions, including antitumoral effects through the modulation of the
farnesyl pyrophosphate synthase (FPPS) activity. To investigate the
relationship between i6A and FPPS, we undertook an inverse virtual
screening computational target searching, testing i6A on a large panel
of 3D protein structures involved in cancer processes. Experimentally,
we performed an NMR investigation of i6A in the presence of FPPS protein.
Both inverse virtual screening and saturation transfer difference
(STD) NMR outcomes provided evidence of the structural interaction
between i6A and FPPS, pointing to i6A as a valuable lead compound
in the search of new ligands endowed with antitumoral potential and
targeting FPPS protein
Designed Glucopeptides Mimetics of Myelin Protein Epitopes As Synthetic Probes for the Detection of Autoantibodies, Biomarkers of Multiple Sclerosis
We previously reported that CSF114Â(Glc) detects diagnostic
autoantibodies in multiple sclerosis sera. We report herein a bioinformatic
analysis of myelin proteins and CSF114Â(Glc), which led to the identification
of five sequences. These glucopeptides were synthesized and tested
in enzymatic assays, showing a common minimal epitope. Starting from
that, we designed an optimized sequence, SP077, showing a higher homology
with both CSF114Â(Glc) and the five sequences selected using the bioinformatic
approach. SP077 was synthesized and tested on 50 multiple sclerosis
patients’ sera, and was able to detect higher antibody titers
as compared to CSF114Â(Glc). Finally, the conformational properties
of SP077 were studied by NMR spectroscopy and structure calculations.
Thus, the immunological activity of SP077 in the recognition of specific
autoantibodies in multiple sclerosis patients’ sera may be
ascribed to both the optimized design of its epitopic region and the
superior surface interacting properties of its C-terminal region