19 research outputs found
Two-dimensional mass spectrometry: new perspectives for tandem mass spectrometry
International audienc
Enhanced rigidity and rupture strength of composite hydrogel networks of bio-inspired block copolymers
<p>We study self-assembled composite networks consisting of silk-like protein fibers dispersed in a soft gel matrix formed by collagen-like block copolymers. Rheological analysis shows that the composite networks have significantly higher storage moduli than either of the single networks. This is caused by bundling of the fibrils due to depletion attraction induced by the collagen-like polymers. Moreover, the soft background network significantly modifies the non-linear response of the fibrillar network; the strain-hardening disappears almost completely and the stress and strain at which the gel breaks increase strongly, resulting in tougher hydrogels.</p>
Two-Dimensional ECD FT-ICR Mass Spectrometry of Peptides and Glycopeptides
2D FT-ICR MS allows the correlation between precursor
and fragment
ions by modulating ion cyclotron radii for fragmentation modes with
radius-dependent efficiency in the ICR cell without the need for prior
ion isolation. This technique has been successfully applied to ionâmolecule
reactions, Collision-induced dissociation and infrared multiphoton
dissociation. In this study, we used electron capture dissociation
for 2D FT-ICR MS for the first time, and we recorded two-dimensional
mass spectra of peptides and a mixture of glycopeptides that showed
fragments that are characteristic of ECD for each of the precursor
ions in the sample. We compare the sequence coverage obtained with
2D ECD FT-ICR MS with the sequence coverage obtained with ECD MS/MS
and compare the sensitivities of both techniques. We demonstrate how
2D ECD FT-ICR MS can be implemented to identify peptides and glycopeptides
for proteomics analysis
Improvement of linear prediction processing of NMR spectra having very low signal-to-noise
Uncovering the Selection Criteria for the Emergence of Multi-Building-Block Replicators from Dynamic Combinatorial Libraries
A family of self-replicating macrocycles
was developed using dynamic
combinatorial chemistry. Replication is driven by self-assembly of
the replicators into fibrils and relies critically on mechanically
induced fibril fragmentation. Analysis of separate dynamic combinatorial
libraries made from one of six peptide-functionalized building blocks
of different hydrophobicity revealed two selection criteria that govern
the emergence of replicators from these systems. First, the replicators
need to have a critical macrocycle size that endows them with sufficient
multivalency to enable their self-assembly into fibrils. Second, efficient
replication occurs only for library members that are of low abundance
in the absence of a replication pathway. This work has led to spontaneous
emergence of replicators with unrivalled structural complexity, being
built from up to eight identical subunits and reaching a MW of up
to 5.6 kDa. The insights obtained in this work provide valuable guidance
that should facilitate future discovery of new complex self-replicating
molecules. They may also assist in the development of new self-synthesizing
materials, where self-assembly drives the synthesis of the very molecules
that self-assemble. To illustrate the potential of this concept, the
present system enables access to self-assembling materials made from
self-synthesizing macrocycles with tunable ring size ranging from
trimers to octamers
Can Two-Dimensional IR-ECD Mass Spectrometry Improve Peptide de Novo Sequencing?
Two-dimensional
mass spectrometry (2D MS) correlates precursor
and fragment ions without ion isolation in a Fourier transform ion
cyclotron resonance mass spectrometer (FTICR MS) for tandem mass spectrometry.
Infrared activated electron capture dissociation (IR-ECD), using a
hollow cathode configuration, generally yields more information for
peptide sequencing in tandem mass spectrometry than ECD (electron
capture dissociation) alone. The effects of the fragmentation zone
on the 2D mass spectrum are investigated as well as the structural
information that can be derived from it. The enhanced structural information
gathered from the 2D mass spectrum is discussed in terms of how de
novo peptide sequencing can be performed with increased confidence.
2D IR-ECD MS is shown to sequence peptides, to distinguish between
leucine and isoleucine residues through the production of <i>w</i> ions as well as between C-terminal (<i>b</i>/<i>c</i>) and N-terminal (<i>y</i>/<i>z</i>) fragments through the use of higher harmonics, and to assign and
locate peptide modifications
NMR WaterLOGSY Reveals Weak Binding of Bisphenol A with Amyloid Fibers of a Conserved 11 Residue Peptide from Androgen Receptor
There is growing evidence that bisphenol A (BPA), a molecule largely released in the environment, has detrimental effects on ecosystems and on human health. It acts as an endocrine disruptor targeting steroid hormone receptors, such as the estrogen receptor (ER), estrogen-related receptor (ERR) and androgen receptor (AR). BPA-derived molecules have recently been shown to interact with the AR N-terminal domain (AR-NTD), which is known to be largely intrinsically disordered. This N-terminal domain contains an 11 residue conserved domain that forms amyloid fibers upon oxidative dimerisation through its strictly conserved Cys240 residue. We investigate here the interaction of BPA, and other potential endocrine disruptors, with AR-NTD amyloid fibers using the WaterLOGSY NMR experiment. We observed a selective binding of these compounds to the amyloid fibers formed by the AR-NTD conserved region and glutamine homopolymers. This observation suggests that the high potency of endocrine disruptors may result, in part, from their ability to bind amyloid forms of nuclear receptors in addition to their cognate binding sites. This property may be exploited to design future therapeutic strategies targeting AR related diseases such as the spinal bulbar muscular atrophy or prostate cancer. The ability of NMR WaterLOGSY experiments to detect weak interactions between small ligands and amyloid fibers may prove to be of particular interest for identifying promising hit molecules