Probing the surface accessibility of proteins with noncovalent receptors and MALDI mass spectrometry

Friess, Sebastian D.; Daniel, Jürg M.; Zenobi, Renato

doi:10.1039/b315380k

Cited by 20 publications

(17 citation statements)

References 92 publications

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“…The purpose of this investigation was to learn more about protein surface recognition by supramolecular building blocks . To this end, we characterised the interactions between four anionic ligands (of varying size, shape, charge and hydrophobicity, Table , Figure ) and one protein—human ubiquitin.…”

Section: Discussionmentioning

confidence: 99%

“…The purpose of this investigation was to learn more about protein surfacer ecognition by supramolecular building blocks. [1,2,27,52] To this end, we characterisedthe interactions between four anionic ligands( of varying size, shape, chargea nd hydrophobicity,T able 1, Figure 1) and one protein-human ubiquitin. With the aid of the binding maps (Figures 6a nd 7) and dissociation constants (Figures 8a nd 9) it was possible to address the question of ligand specificity.L igand 4PSA, the smallest and simplesto ft he four,w as the most specific, with ab inding site focusedo nt he "arginine face" at which favourable hydrophobic, salt-bridge and cation-p interactions may form.…”

Section: Discussionmentioning

confidence: 99%

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Protein Camouflage: Supramolecular Anion Recognition by Ubiquitin

et al. 2016

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Progress in the field of bio-supramolecular chemistry, the bottom-up assembly of protein-ligand systems, relies on a detailed knowledge of molecular recognition. To address this issue, we have characterised complex formation between human ubiquitin (HUb) and four supramolecular anions. The ligands were: pyrenetetrasulfonic acid (4PSA), p-sulfonato-calix[4]arene (SCLX4), bisphosphate tweezers (CLR01) and meso-tetrakis (4-sulfonatophenyl)porphyrin (TPPS), which vary in net charge, size, shape and hydrophobicity. All four ligands induced significant changes in the HSQC spectrum of HUb. Chemical shift perturbations and line-broadening effects were used to identify binding sites and to quantify affinities. Supporting data were obtained from docking simulations. It was found that these weakly interacting ligands bind to extensive surface patches on HUb. A comparison of the data suggests some general indicators for the protein-binding specificity of supramolecular anions. Differences in binding were observed between the cavity-containing and planar ligands. The former had a preference for the arginine-rich, flexible C terminus of HUb.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Protein Camouflage: Supramolecular Anion Recognition by Ubiquitin

et al. 2016

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“…Although noncovalent intermolecular interactions are usually lost during MALDI sample preparation or during the laser desorption/ionization step, some special techniques permit detection of noncovalent complexes, e.g., first shot experiments [21], particular laser/matrix combinations, and varying the sample preparation conditions [22]. By far the most promising and most general approach is the stabilization of the complex subunits by chemical cross-linking (XL) before MALDI-MS. XL prevents the protein complexes from being disrupted throughout the sample preparation and the desorption/ionization processes [23].…”

Section: E Lectrospray Is An Exceptionally Soft Ionizationmentioning

confidence: 99%

Probing the hydrophobic effect of noncovalent complexes by mass spectrometry

Bich

Baer

Jecklin

et al. 2010

J. Am. Soc. Mass Spectrom.

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The study of noncovalent interactions by mass spectrometry has become an active field of research in recent years. The role of the different noncovalent intermolecular forces is not yet fully understood since they tend to be modulated upon transfer into the gas phase. The hydrophobic effect, which plays a major role in protein folding, adhesion of lipid bilayers, etc., is absent in the gas phase. Here, noncovalent complexes with different types of interaction forces were investigated by mass spectrometry and compared with the complex present in solution. Creatine kinase (CK), glutathione S-transferase (GST), ribonuclease S (RNase S), and leucine zipper (LZ), which have dissociation constants in the nM range, were studied by native nanoelectrospray mass spectrometry (nanoESI-MS) and matrix-assisted laser desorption/ ionization mass spectrometry (MALDI-MS) combined with chemical cross-linking (XL). Complexes interacting with hydrogen bonds survived the transfer into gas phase intact and were observed by nanoESI-MS. Complexes that are bound largely by the hydrophobic effect in solution were not detected or only at very low intensity. Complexes with mixed polar and hydrophobic interactions were detected by nanoESI-MS, most likely due to the contribution from polar interactions. All noncovalent complexes could easily be studied by XL MALDI-MS, which demonstrates that the noncovalently bound complexes are conserved, and a real "snap-shot" of the situation in solution can be obtained. (J Am Soc Mass Spectrom 2010, 21, 286 -289) © 2010 American Society for Mass Spectrometry E lectrospray is an exceptionally soft ionization technique, which has allowed the observation of numerous noncovalent complexes, including protein-protein, protein-small molecule, and protein-DNA complexes [1,2]. A major question is still whether the information obtained from gas-phase results is representative of the species present in solution. The term "noncovalent bonding" in biochemistry generally summarizes three types of intermolecular forces: electrostatic interactions (e.g., salt bridges), dipolar interactions (e.g., hydrogen bonds), and van der Waals interactions (e.g., hydrophobic interactions) [3]. In addition, protein-water interactions often play a major role in complex stabilization. In solution, hydrophobic interactions are very weak compared with the hydrogen bonds between water molecules. Hence, it is not the hydrophobic forces that are the actual reason for the interaction of nonpolar binding partners, but rather the surrounding water molecules that "force" hydrophobic binding partners to aggregate. This solvent-driven process is called the hydrophobic effect, and plays a major role in protein folding, adhesion of lipid bilayers, partitioning effects of drugs and metabolites, and many other aggregation phenomena in chemistry and biology [4][5][6]. The hydrophobic effect is defined by the thermodynamics of mixing hydrophobic compounds with water, and is dominated by large, entropic factors [4,7]. Obviously, in the absence of a hydr...

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“…Mass spectrometry (MS) has become a powerful tool for the elucidation of large biomolecules and their noncovalent complexes after soft ionization techniques, especially electrospray ionization (ESI) and matrix‐assisted laser desorption/ionization (MALDI), have made possible the generation of gas‐phase ions from such species . These ionization techniques have also resulted in widespread MS applications to polymer research, where MS is vital for the characterization of the chemical compositions and functionality distributions of synthetic polymers .…”

Section: Introductionmentioning

confidence: 99%

Strong ionic interactions in noncovalent complexes between poly(ethylene imine), a cationic electrolyte, and Cibacron Blue, a nucleotide mimic – implications for oligonucleotide vectors

2014

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Cationic polymers can bind DNA to form polyplexes, which are noncovalent complexes used for gene delivery into the targeted cells. For more insight on such biologically relevant systems, the noncovalent complexes between the cationic polymer poly(ethylene imine) (PEI) and the nucleotide mimicking dye Cibacron Blue F3G-A (CB) were investigated using mass spectrometry methods. Two PEIs of low molecular weight were utilized (Mn ≈ 423 and 600 Da). The different types of CB anions produced by Na(+)/H(+) exchanges on the three sulfonic acid groups of CB and their dehydrated counterparts were responsible for complex formation with PEI. The CB anions underwent noncovalent complex formation with protonated, but not with sodiated PEI. A higher proportion of cyclic oligomers were detected in PEI423 than PEI600, but both architectures formed association products with CB. Tandem mass spectrometry studies revealed a significantly stronger noncovalent interaction between PEI and dehydrated CB than between PEI and intact CB.

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Probing the surface accessibility of proteins with noncovalent receptors and MALDI mass spectrometry

Cited by 20 publications

References 92 publications

Protein Camouflage: Supramolecular Anion Recognition by Ubiquitin

Protein Camouflage: Supramolecular Anion Recognition by Ubiquitin

Probing the hydrophobic effect of noncovalent complexes by mass spectrometry

Strong ionic interactions in noncovalent complexes between poly(ethylene imine), a cationic electrolyte, and Cibacron Blue, a nucleotide mimic – implications for oligonucleotide vectors

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