2 research outputs found
Cyclodextrin-Adamantane Host–Guest Interactions on the Surface of Biocompatible Adamantyl-Modified Glycodendrimers
A series of adamantyl-modified glycodendrimers
(<b>mPPI-Gx-AdaA-C</b>) was prepared in a two-step synthesis
using two efficient reactions:
(1) urea bond formation from amine and isocyanate and (2) reductive
amination. <sup>1</sup>H NMR spectroscopy (host guest titration and
ROESY experiments) was used to evaluate the graded effect of steric
hindrance as a function of the number and type of oligosaccharide
molecules and of the number of adamantyl (Ada) units on the complexation
with monomeric β-cyclodextrin (β-CD). Glycosylated fourth
generation PPIs showing an average substitution in adamantyl groups
of 13% were found to interact with β-CD effectively, and were
considered as candidates for further complexation studies with a polymeric
cyclodextrin derivative (<i>poly-</i>β-CD). The host–guest
interaction features of the maltosylated dense shell glycodendrimer
along with the low cytotoxicity provided the rational basis for the
use of these adamantyl-functionalized glycodendrimers in the design
of supramolecular systems potentially useful as healthcare materials
Laser-Induced Liquid Bead Ion Desorption Mass Spectrometry: An Approach to Precisely Monitor the Oligomerization of the β-Amyloid Peptide
In the present work, the recently developed laser-induced
liquid
bead ion desorption mass spectrometry (LILBID MS) is applied as a
novel technique to study Aβ oligomerization, thought to be crucial
in Alzheimer’s disease (AD). The characterization of the earliest
nucleation events of this peptide necessitates the application of
several techniques to bridge the gap between small oligomers and large
fibrils. We precisely monitored in time the transformation of monomeric
Aβ (1-42) into oligomeric Aβ<sub><i>n</i></sub> (<i>n</i> < 20) and its dependence on concentration
and agitation. The distribution shows signs of the hexamer being crucial
in the assembly process. The intensity of the monomer decreases in
time with a time constant of about 9 h. After a lag time of around
10 h, a phase transition occurred in which the total ion current of
the oligomers goes to nearly zero. In this late stage of aggregation,
protofibrils are formed and mass spectrometry is no longer sensitive.
Here fluorescence correlation spectroscopy (FCS) and transmission
electron microscopy (TEM) are complementary tools for detection and
size characterization of these large species. We also utilized the
oligomers of Aβ (1-42) as a model of the corresponding <i>in vivo</i> process to screen the efficacy and specificity of
small molecule inhibitors of oligomerization. The LILBID results are
in excellent agreement with condensed phase behavior determined in
other studies. Our data identified LILBID MS as a powerful technique
that will advance the understanding of peptide oligomerization in
neurodegenerative diseases and represents a powerful tool for the
identification of small oligomerization inhibitors