We present the use of drug-like molecules as a traveling wave (T-wave) ion mobility (IM) calibration sample set, covering m/z range 122.1-609.3, nitrogen collision cross-section (Ω(N(2))) 124.5-254.3 Å(2) and helium (Ω(He)) 63.0-178.8 Å(2). Absolute Ω(N(2)) Ω(He) values for calibrants two diastereomers were measured using drift-tube instrument with radio frequency (RF) confinement. T-wave drift-times protonated betamethasone dexamethasone are reproducibly different. Calibration these yields...

Abstract Amyloid fibrils are insoluble protein aggregates comprised of highly ordered β‐sheet structures and they involved in the pathology amyloidoses, such as Alzheimer’s disease. A supramolecular strategy is presented for inhibiting amyloid fibrillation by using cucurbit[7]uril (CB[7]). CB[7] prevents insulin β‐amyloid capturing phenylalanine (Phe) residues, which crucial to hydrophobic interactions formed during fibrillation. These results suggest that Phe‐specific binding can modulate...

This work presents a systematic study on the host–guest interactions between macrocyclic host molecule cucurbit[7]uril (CB[7]) and amino acids (AAs) including three basic AAs (Lys, Arg, His) aromatic (Phe, Tyr, Trp) to elucidate origin of high selectivity CB[7] toward AA residues in proteins. Complex formation each was examined solution (by isothermal titration calorimetry NMR) as well gas phase ion mobility mass spectrometry collision-induced dissociation), results were further combined...

A number of phosphatidylcholine (PC) cations spanning a mass range 400−1000 Da are investigated using electrospray ionization spectrometry coupled with traveling wave ion mobility (TWIMS). high correlation between and is demonstrated saturated in N2. significant deviation from this mass−mobility line observed for the unsaturated PC cation. We found that double bond acyl chain causes 5% reduction drift time. The time reduced at rate ∼1% each additional bond. Theoretical collision cross...

Regulation of amyloid-β (Aβ) aggregation by metal ions and proteins is essential for understanding the pathology Alzheimer's disease (AD). Human serum albumin (HSA), a regulator protein transportation, can modulate metal-Aβ interactions Aβ in human fluid; however, molecular mechanisms such activities remain unclear. Herein, we report molecular-level complexation between Zn(II), Cu(II), Aβ, HSA, which able to alter cytotoxicity peptides induce their cellular transportation. In addition,...

Structural characterization of intrinsically disordered proteins (IDPs) has been a major challenge in the field protein science due to limited capabilities obtain full-length high-resolution structures. Native ESI-MS with top-down MS was utilized structural features protein-ligand binding for Parkinson's disease-related protein, α-synuclein (αSyn), which is natively unstructured. Binding heavy metals implicated accelerated formation αSyn aggregation. Using Fourier transform ion cyclotron...

Fibrillar amyloid aggregates are the pathological hallmarks of multiple neurodegenerative diseases. The amyloid-β (1-42) protein, in particular, is a major component senile plaques brains patients with Alzheimer's disease and primary target for treatment. Determining essential domains that facilitate its oligomerization critical development aggregation inhibitors as potential therapeutic agents. In this study, we identified three key hydrophobic sites (17LVF19, 32IGL34, 41IA42) on...

A number of tertiary amine and quaternary ammonium cations spanning a mass range 60−146 amu (trimethylamine, tetramethylammonium, trimethylethylammonium, N,N-dimethylaminoethanol, choline, N,N-dimethylglycine, betaine, acetylcholine, (3-carboxypropyl)trimethylammonium) were investigated using electrospray ionization ion mobility spectrometry. Measured mobilities demonstrate high correlation between in N2. In addition, identical within experimental uncertainties are observed for structurally...

Ultrahigh-resolution mass spectrometry has allowed the determination of elemental formulas compounds comprising crude oils. However, elucidating molecular structures remains an analytical challenge. Herein, we propose and demonstrate approach combining ion mobility (IM-MS), ultrahigh-resolution spectrometry, theoretical collisional cross-section (CCS) calculations to determine aromatic found in The is composed three steps. First, chemical are suggested based on determined from spectra....

α-Synuclein (αSyn) is an intrinsically disordered protein, the aggregation of which highly related to pathology diverse α-synucleinopathies. Various hard divalent metal cations have been shown affect αSyn aggregation. Especially, Ca2+ suggested be a crucial ion due its physiological relevance However, molecular origin mediated by ions not fully elucidated. In this study, we revealed that had almost identical influences on Based these similarities, role was investigated as representative ion....

Abstract Development of versatile ruthenium olefin-metathesis catalysts with high activity, stability, and selectivity is a continuous challenge. Here we report highly controllable using readily accessible N -vinylsulfonamides as carbene precursors. Catalyst initiation rates were controlled in straightforward manner, from latent to fast initiating, through the facile modulation -vinylsulfonamide ligands. Trifluoromethanesulfonamide-based initiated ultrarapidly even at temperatures low −60 °C...

Amyloid proteins that undergo self-assembly to form insoluble fibrillar aggregates have attracted much attention due their role in biological and pathological significance amyloidosis. This study aims understand the amyloid aggregation dynamics of insulin (INS) H2O using two-dimensional infrared (2D-IR) spectroscopy. Conventional IR studies been performed D2O avoid spectral congestion despite distinct H-D isotope effects. We observed a slowdown INS fibrillation process compared H2O. The...

An investigation of the host–guest chemistry cucurbit[n]uril (CB[n], n = 6 and 7) with α,ω-alkyldiammonium guests (H2N(CH2)xNH2, x 4, 6, 8, 10, 12) both in solution gas phase elucidates their intrinsic properties contribution solvent water. Isothermal titration calorimetry nuclear magnetic resonance measurements indicate that all alkyldiammonium cations have inclusion interactions CB[n] except for CB[7]–tetramethylenediamine complex aqueous solution. The electrospray ionization mixtures...

Mass spectrometry (MS)-based analysis using enzymatic digestion is widely used for protein sequencing and characterization. The large number of peptides generated from proteolysis, however, suppresses the signal with low ionization efficiency, thus precluding their observation analysis. This study describes a technique improved peptic by adding synthetic receptor cucurbit[7]uril (CB[7]), which binds selectively to N-terminal aromatic residues. Capturing phenylalanine (Phe) CB[7] enhances...

Theoretical collision cross section calculations revisited for reliable ion structural studies.

Amyloidosis is a clinical disorder implicated with the formation of toxic amyloid aggregates. Despite their pathological significance, it challenging to define structural characteristics oligomers owing metastable nature. Herein, we report and mechanistic investigations human islet polypeptide (hIAPP) oligomers, found in type II diabetes mellitus, both absence presence disease-relevant metal ions [i.e., Cu(ii) Zn(ii)]. These show suppressive effects on hIAPP fibrillation facilitate...

An accurate theoretical collision cross section calculation method in nitrogen was developed for reliable structural ion mobility mass spectrometry.

Oxidative stresses from irritants such as hydrogen peroxide and ozone (O3) can cause dysfunction of the pulmonary surfactant (PS) layer in human lung, resulting chronic diseases respiratory tract. For identification structural changes protein B (SP-B) due to heterogeneous reaction with O3, field-induced droplet ionization (FIDI) mass spectrometry has been utilized. FIDI is a soft method which ions are extracted surface microliter-volume droplets. We report structurally specific oxidative...

The gas phase host-guest chemistry between cucurbit[6]uril (CB[6]) and peptide is investigated using electrospray ionization mass spectrometry (ESI-MS). CB[6] exhibits a high preference to interacting with Lys residue in forming CB[6]-peptide complex. Collisionally activated complexes of peptides yield common highly selective fragment product at m/z 549.2, corresponding the doubly charged complex 5-iminiopentylammonium (5IPA). process involves formation an internal iminium ion, which results...

Abstract Nitric oxide (NO) is a gaseous molecule intricately implicated in oncologic processes, encompassing the modulation of angiogenesis and instigating apoptosis. Investigation antitumor effects NO currently underway, necessitating detailed understanding its cellular‐level reactions. Regulating behavior radical species has been significant challenge, primarily due to instability aqueous environments by rapid O 2 ‐induced degradation. In this study, we devised an electrochemical platform...