Quartz Microbalance Technology for Probing Biomolecular Interactions

Heller, Gabriella T.; Mercer-Smith, Alison; Johal, Malkiat S.

doi:10.1007/978-1-4939-2425-7_9

Cited by 7 publications

(4 citation statements)

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“…An initial hit was optimized to produce the small molecule YK-4-279, with a reported affinity of 10 μM, which showed in vitro and in vivo inhibition of the RNA helicase A binding ability of EWS–FLI1. Like SPR, other surface-based techniques including bio-layer interferometry (BLI) [ 116 ] and quartz crystal microbalance (QCM) [ 117 ] are extremely sensitive and well suited to study disordered protein interactions with small molecules [ 25 ]. We also point out, however, that with any surface-based technique, one should carefully minimize any non-specific interaction with the sensor or the tip, or to account for them appropriately in the analysis [ 118 ].…”

Section: Methods Of Characterizing Ligand Interactions With Monomericmentioning

confidence: 99%

Methods of probing the interactions between small molecules and disordered proteins

Heller

Aprile

Vendruscolo

2017

Cell. Mol. Life Sci.

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It is generally recognized that a large fraction of the human proteome is made up of proteins that remain disordered in their native states. Despite the fact that such proteins play key biological roles and are involved in many major human diseases, they still represent challenging targets for drug discovery. A major bottleneck for the identification of compounds capable of interacting with these proteins and modulating their disease-promoting behaviour is the development of effective techniques to probe such interactions. The difficulties in carrying out binding measurements have resulted in a poor understanding of the mechanisms underlying these interactions. In order to facilitate further methodological advances, here we review the most commonly used techniques to probe three types of interactions involving small molecules: (1) those that disrupt functional interactions between disordered proteins; (2) those that inhibit the aberrant aggregation of disordered proteins, and (3) those that lead to binding disordered proteins in their monomeric states. In discussing these techniques, we also point out directions for future developments.

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Section: Methods Of Characterizing Ligand Interactions With Monomericmentioning

confidence: 99%

Methods of probing the interactions between small molecules and disordered proteins

Heller

Aprile

Vendruscolo

2017

Cell. Mol. Life Sci.

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“…Subsequently, dynamic adsorption behaviors of InsP 6 on the PNI- co -ATBA 0.2 surface were monitored using a quartz–crystal microbalance with dissipation (QCM-D), which simultaneously measured the real-time variation in resonance frequency (Δ f ) and energy dissipation (Δ D ) when the mass adsorbed on an oscillated piezoelectric crystal changes . As shown in Figure A, InsP 6 displayed a rapid dynamic adsorption on the PNI- co -ATBA 0.2 surface with a maximal Δ f of −27.5 Hz after 2 min, corresponding to an adsorption quantity of 162 ng cm –2 according to the Sauerbrey equation . By comparison, when the PNIPAAm homopolymer or ATBA-monolayer-modified QC resonator was introduced in the control experiment, the frequency change caused by InsP 6 adsorption (Δ f : 0.6 or 3.9 Hz, respectively) was substantially lower than that on the PNI- co -ATBA 0.2 surface.…”

Section: Resultsmentioning

confidence: 99%

Developing an Inositol-Phosphate-Actuated Nanochannel System by Mimicking Biological Calcium Ion Channels

Lü

Tang

Chen

et al. 2017

ACS Appl. Mater. Interfaces

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In eukaryotic cells, ion channels, which ubiquitously present as polypeptides or proteins, usually regulate the ion transport across biological membranes by conformational switching of the channel proteins in response to the binding of diverse signaling molecules (e.g., inositol phosphate, abbreviated to InsP). To mimic the gating behaviors of natural Ca channels manipulated by InsPs, a smart poly[(N-isopropylacrylamide-co-4-(3-acryloylthioureido) benzoic acid)] (denoted as PNI-co-ATBA) was integrated onto a porous anodic alumina (PAA) membrane, building an InsP-actuated nanochannel system. Driven by the intensive hydrogen bonding complexation of ATBA monomer with InsP, the copolymer chains displayed a remarkable and reversible conformational transition from a contracted state to a swollen one, accompanied with significant changes in surface morphology, wettability, and viscoelasticity. Benefiting from these features, dynamic gating behaviors of the nanochannels located on the copolymer-modified PAA membrane could be precisely manipulated by InsPs, reflected as a satisfactory linear relationship between real-time variation in transmembrane ionic current and the InsP concentration over a wide range from 1 nmol L to 10 μmol L, as well as a clear discrimination among InsP, InsP, and InsP. This study indicates the great potential of biomolecule-responsive polymers in the fabrication of biomimetic ion nanochannels and other nanoscale biodevices.

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“…It is an acoustic sensor based on a piezoelectric crystal, consisting of a thin quartz disk with electrodes plated on both disks connected to an oscillating circuit. Binding of the analyte to the immobilized ligand results in a resonance frequency shift that is recorded over time and generates sensorgrams from which the equilibrium binding constants and affinity constants can be derived [41][42][43][44].…”

Section: Identification Of Protein Partnerships and Characterization ...mentioning

confidence: 99%

Targeting Protein–Protein Interfaces with Peptides: The Contribution of Chemical Combinatorial Peptide Library Approaches

Monti

Vitagliano

Caporale

et al. 2023

IJMS

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Protein–protein interfaces play fundamental roles in the molecular mechanisms underlying pathophysiological pathways and are important targets for the design of compounds of therapeutic interest. However, the identification of binding sites on protein surfaces and the development of modulators of protein–protein interactions still represent a major challenge due to their highly dynamic and extensive interfacial areas. Over the years, multiple strategies including structural, computational, and combinatorial approaches have been developed to characterize PPI and to date, several successful examples of small molecules, antibodies, peptides, and aptamers able to modulate these interfaces have been determined. Notably, peptides are a particularly useful tool for inhibiting PPIs due to their exquisite potency, specificity, and selectivity. Here, after an overview of PPIs and of the commonly used approaches to identify and characterize them, we describe and evaluate the impact of chemical peptide libraries in medicinal chemistry with a special focus on the results achieved through recent applications of this methodology. Finally, we also discuss the role that this methodology can have in the framework of the opportunities, and challenges that the application of new predictive approaches based on artificial intelligence is generating in structural biology.

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Quartz Microbalance Technology for Probing Biomolecular Interactions

Cited by 7 publications

References 1 publication

Methods of probing the interactions between small molecules and disordered proteins

Methods of probing the interactions between small molecules and disordered proteins

Developing an Inositol-Phosphate-Actuated Nanochannel System by Mimicking Biological Calcium Ion Channels

Targeting Protein–Protein Interfaces with Peptides: The Contribution of Chemical Combinatorial Peptide Library Approaches

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