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Chemical Communications (Cambridge,... Jun 2018Structural differences in pathological and functional amyloid fibrils have been investigated by Raman microspectroscopy. Second-derivative analyses of amide-I and...
Structural differences in pathological and functional amyloid fibrils have been investigated by Raman microspectroscopy. Second-derivative analyses of amide-I and amide-III bands distinguish parallel in-register β-sheets from a β-solenoid. Further, spatially resolved Raman spectra reveal molecular heterogeneity in amyloid structures.
Topics: Amides; Amyloid beta-Peptides; Humans; Particle Size; Protein Conformation; Spectrum Analysis, Raman; Surface Properties
PubMed: 29774336
DOI: 10.1039/c8cc03217c -
Journal of Nanobiotechnology Dec 2022Extracellular Vesicles (EVs) are sub-micrometer lipid-bound particles released by most cell types. They are considered a promising source of cancer biomarkers for liquid...
BACKGROUND
Extracellular Vesicles (EVs) are sub-micrometer lipid-bound particles released by most cell types. They are considered a promising source of cancer biomarkers for liquid biopsy and personalized medicine due to their specific molecular cargo, which provides biochemical information on the state of parent cells. Despite this potential, EVs translation process in the diagnostic practice is still at its birth, and the development of novel medical devices for their detection and characterization is highly required.
RESULTS
In this study, we demonstrate mid-infrared plasmonic nanoantenna arrays designed to detect, in the liquid and dry phase, the specific vibrational absorption signal of EVs simultaneously with the unspecific refractive index sensing signal. For this purpose, EVs are immobilized on the gold nanoantenna surface by immunocapture, allowing us to select specific EV sub-populations and get rid of contaminants. A wet sample-handling technique relying on hydrophobicity contrast enables effortless reflectance measurements with a Fourier-transform infrared (FTIR) spectro-microscope in the wavelength range between 10 and 3 µm. In a proof-of-principle experiment carried out on EVs released from human colorectal adenocarcinoma (CRC) cells, the protein absorption bands (amide-I and amide-II between 5.9 and 6.4 µm) increase sharply within minutes when the EV solution is introduced in the fluidic chamber, indicating sensitivity to the EV proteins. A refractive index sensing curve is simultaneously provided by our sensor in the form of the redshift of a sharp spectral edge at wavelengths around 5 µm, where no vibrational absorption of organic molecules takes place: this permits to extract of the dynamics of EV capture by antibodies from the overall molecular layer deposition dynamics, which is typically measured by commercial surface plasmon resonance sensors. Additionally, the described metasurface is exploited to compare the spectral response of EVs derived from cancer cells with increasing invasiveness and metastatic potential, suggesting that the average secondary structure content in EVs can be correlated with cell malignancy.
CONCLUSIONS
Thanks to the high protein sensitivity and the possibility to work with small sample volumes-two key features for ultrasensitive detection of extracellular vesicles- our lab-on-chip can positively impact the development of novel laboratory medicine methods for the molecular characterization of EVs.
Topics: Humans; Extracellular Vesicles; Liquid Biopsy; Neoplasms; Cell Culture Techniques; Proteins; Amides
PubMed: 36514065
DOI: 10.1186/s12951-022-01693-2 -
ChemistryOpen Oct 2022Introduction of adamantane moieties on diamondoids such as adamantane, 2-azaadamantane or diamantane by amide formation and reduction to the corresponding amine was...
Introduction of adamantane moieties on diamondoids such as adamantane, 2-azaadamantane or diamantane by amide formation and reduction to the corresponding amine was performed in a straightforward and easy way by amidation under Schotten-Baumann conditions and reduction with BH ⋅ THF. The obtained amides and amines were studied in terms of structural properties towards the perspective of transformation into nanodiamonds. Crystal structure and dynamic NMR experiments of the most crowded amide obtained gave structural insights into the effect of bulkiness and steric strain on out-of-planarity of amide bonds (16.0°) and the kinetics and thermodynamics of amide bond rotation (ΔG =11.5-13.3 kcal ⋅ mol ).
Topics: Adamantane; Amides; Amines; Nanodiamonds; Thermodynamics
PubMed: 35243816
DOI: 10.1002/open.202200031 -
Molecules (Basel, Switzerland) Nov 2018Not all amide bonds are created equally. The purpose of the present paper is the reinterpretation of the amide group by means of two concepts: amidicity and...
Not all amide bonds are created equally. The purpose of the present paper is the reinterpretation of the amide group by means of two concepts: amidicity and carbonylicity. These concepts are meant to provide a new viewpoint in defining the stability and reactivity of amides. With the help of simple quantum-chemical calculations, practicing chemists can easily predict the outcome of a desired process. The main benefit of the concepts is their simplicity. They provide intuitive, but quasi-thermodynamic data, making them a practical rule of thumb for routine use. In the current paper we demonstrate the performance of our methods to describe the chemical character of an amide bond strength and the way of its activation methods. Examples include transamidation, acyl transfer and amide reductions. Also, the method is highly capable for simple interpretation of mechanisms for biological processes, such as protein splicing and drug mechanisms. Finally, we demonstrate how these methods can provide information about photo-activation of amides, through the examples of two caged neurotransmitter derivatives.
Topics: Algorithms; Amides; Chemistry Techniques, Synthetic; Models, Chemical; Thermodynamics
PubMed: 30400217
DOI: 10.3390/molecules23112859 -
Nature Communications Aug 2023Thioamides are an important, but a largely underexplored class of amide bioisostere in peptides. Replacement of oxoamide units with thioamides in peptide therapeutics is...
Thioamides are an important, but a largely underexplored class of amide bioisostere in peptides. Replacement of oxoamide units with thioamides in peptide therapeutics is a valuable tactic to improve biological activity and resistance to enzymatic hydrolysis. This tactic, however, has been hampered by insufficient methods to introduce thioamide bonds into peptide or protein backbones in a site-specific and stereo-retentive fashion. In this work, we developed an efficient and mild thioacylation method to react nitroalkanes with amines directly in the presence of elemental sulfur and sodium sulfide to form a diverse range of thioamides in high yields. Notably, this convenient method can be employed for the controlled thioamide coupling of multifunctionalized peptides without epimerization of stereocenters, including the late stage thioacylation of advanced compounds of biological and medicinal interest. Experimental interrogation of postulated mechanisms currently supports the intermediacy of thioacyl species.
Topics: Thioamides; Amides; Peptides; Amines
PubMed: 37532721
DOI: 10.1038/s41467-023-40334-6 -
Medicine Jun 2017Myoclonus, a common complication during intravenous induction with etomidate, is bothersome to both anesthesiologists and patients. This study explored the preventive... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Myoclonus, a common complication during intravenous induction with etomidate, is bothersome to both anesthesiologists and patients. This study explored the preventive effect of pretreatment with propofol on etomidate-related myoclonus.
METHODS
This was a prospective, double-blind, clinical, randomized controlled study. Totally, 363 patients who were scheduled for a short-duration, painless gastrointestinal endoscopy were divided into 5 groups. Four groups received 0 mg/kg (E group), 0.25 mg/kg (LPE group), 0.50 mg/kg (MPE group), or 0.75 mg/kg (HPE group) propofol pretreatment before etomidate anesthesia. Another group only received 1 to 2 mg/kg of propofol (P group) as anesthesia. The incidence and severity of myoclonus, patient circulation and respiratory status, and intraoperative and postoperative complications were recorded.
RESULTS
The incidence of myoclonus in the LPE group (26.8%), MPE group (16.4%), HPE group (14.9%), and P group (0) was lower than the E group (48.6%, P < .05). The incidence of grade 1, 2, and 3 of myoclonus in the LPE group, MPE group, HPE group, and P group was significantly lower than the E group, and that in the P group was lower than the LPE group (P < .05). The incidence of hypoxemia in the P group was higher than the E group, and the incidence of adverse events in the HPE group and P group was lower than the E group (P < .05).
DISCUSSION
Pretreatment with propofol was feasible for preventing etomidate-related myoclonus. Furthermore, as propofol dosage increased, its effect on reducing the incidence and severity of myoclonic movements induced by etomidate increased.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anesthetics, Intravenous; Dose-Response Relationship, Drug; Double-Blind Method; Etomidate; Female; Gastroscopy; Hemodynamics; Humans; Incidence; Male; Middle Aged; Myoclonus; Postoperative Complications; Propofol; Respiration; Severity of Illness Index; Time Factors; Young Adult
PubMed: 28658112
DOI: 10.1097/MD.0000000000007212 -
Proceedings of the National Academy of... Nov 2020Folding and other protein self-assembly processes are driven by favorable interactions between O, N, and C unified atoms of the polypeptide backbone and side chains....
Folding and other protein self-assembly processes are driven by favorable interactions between O, N, and C unified atoms of the polypeptide backbone and side chains. These processes are perturbed by solutes that interact with these atoms differently than water does. Amide NH···O=C hydrogen bonding and various π-system interactions have been better characterized structurally or by simulations than experimentally in water, and unfavorable interactions are relatively uncharacterized. To address this situation, we previously quantified interactions of alkyl ureas with amide and aromatic compounds, relative to interactions with water. Analysis yielded strengths of interaction of each alkylurea with unit areas of different hybridization states of unified O, N, and C atoms of amide and aromatic compounds. Here, by osmometry, we quantify interactions of 10 pairs of amides selected to complete this dataset. An analysis yields intrinsic strengths of six favorable and four unfavorable atom-atom interactions, expressed per unit area of each atom and relative to interactions with water. The most favorable interactions are spO-spC (lone pair-π, presumably -π*), spC-spC (π-π and/or hydrophobic), spO-spN (hydrogen bonding) and spC-spC (CH-π and/or hydrophobic). Interactions of spC with itself (hydrophobic) and with spN are modestly favorable, while spN interactions with spN and with amide/aromatic spC are modestly unfavorable. Amide spO-spO interactions and spO-spC interactions are more unfavorable, indicating the preference of amide spO to interact with water. These intrinsic interaction strengths are used to predict interactions of amides with proteins and chemical effects of amides (including urea, -ethylpyrrolidone [NEP], and polyvinylpyrrolidone [PVP]) on protein stability.
Topics: Amides; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Models, Theoretical; Nitrogen; Oxygen; Protein Stability; Proteins; Thermodynamics; Water
PubMed: 33087561
DOI: 10.1073/pnas.2012481117 -
BMC Geriatrics Jan 2024Etomidate has been advocated for anesthesia in older and critically ill patients because of its hemodynamic stability. Clinical studies have shown that dexmedetomidine... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of dexmedetomidine combined with etomidate on postoperative cognitive function in older patients undergoing total intravenous anaesthesia: a randomized, double-blind, controlled trial.
BACKGROUND
Etomidate has been advocated for anesthesia in older and critically ill patients because of its hemodynamic stability. Clinical studies have shown that dexmedetomidine has neuroprotective and anti-inflammatory properties and improves postoperative cognitive dysfunction in older patients. The present study was to evaluate the effects of the combination of etomidate and dexmedetomidine with different anaesthesia time on postoperative cognitive function in older patients.
METHODS
A total of 132 older patients undergoing ureteroscopic holmium laser lithotripsy were randomly divided into EN group and ED group equally. Patients whose surgery time was less than or equal to 1 h in each group were allocated to short-time surgery group (EN group and ED group), and whose surgery time was more than 1h were allocated to long-term surgery group (EN group and ED group). The primary outcome was the score of the Mini-Mental State Examination. The secondary outcomes were State-Trait Anxiety Inventory scores, Riker sedation agitation scores, Zung Self-Rating Depression Scale scores, the memory span for Arabic numerals, the plasma concentrations of S-100 calcium-binding protein B and neuron specific enolase, the time to spontaneous respiration, recovery, and extubation.
RESULTS
The MMSE scores at t were higher in ED and ED groups than in EN and EN groups (p<0.05). Compared with ED and ED groups, the ZSDS scores, the S-AI scores and the T-AI scores at t were higher in EN and EN groups (p<0.05), respectively. The recalled Arabic numbers at t were higher in ED group than in EN group (p<0.05). The plasma concentration of S-100β at t in EN group and t in EN group were higher than that in ED and ED groups (p<0.05), respectively. Compared with ED and ED groups, the plasma concentrations of NSE were higher at t in EN group and t in EN group (p<0.05), respectively.
CONCLUSION
The administration of dexmedetomidine could improve postoperative cognitive dysfunction, emergence agitation, depression and anxiety, attenuate the plasma concentrations of S-100β and NSE in older patients undergoing total intravenous anaesthesia with etomidate.
TRIAL REGISTRATION
Registration number: ChiCTR1800015421, Date: 29/03/2018.
Topics: Humans; Aged; Dexmedetomidine; Etomidate; Postoperative Cognitive Complications; S100 Calcium Binding Protein beta Subunit; Anesthesia, Intravenous; Cognition; Double-Blind Method
PubMed: 38273248
DOI: 10.1186/s12877-024-04726-7 -
The Cochrane Database of Systematic... Jul 2015There is increasing evidence that propofol is efficacious and safe for procedural sedation (PS) in the emergency department (ED) setting. However, propofol has a narrow... (Review)
Review
BACKGROUND
There is increasing evidence that propofol is efficacious and safe for procedural sedation (PS) in the emergency department (ED) setting. However, propofol has a narrow therapeutic window and lacks of a reversal agent. The aim of this review was to cohere the evidence base regarding the efficacy and safety profile of propofol when used in the ED setting for PS.
OBJECTIVES
To identify and evaluate all randomized controlled trials (RCTs) comparing propofol with alternative drugs (benzodiazepines, barbiturates, etomidate and ketamine) used in the ED setting for PS.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9), MEDLINE (1950 to September week 2 2013) and EMBASE (1980 to week 2 2013). We searched the Current Controlled Trials metaRegister of Clinical Trials (compiled by Current Science) (September 2013). We checked the reference lists of trials and contacted trial authors. We imposed no language restriction. We re-ran the search in February 2015. We will deal with the one study awaiting classification when we update the review.
SELECTION CRITERIA
RCTs comparing propofol to alternative drugs (benzodiazepines, barbiturates, etomidate and ketamine) used in the ED setting for PS in participants of all ages.
DATA COLLECTION AND ANALYSIS
Two authors independently performed data extraction. Two authors performed trial quality assessment. We used mean difference (MD), odds ratio (OR) and 95% confidence intervals (CI) to measure effect sizes. Two authors independently assessed and rated the methodological quality of each trial using The Cochrane Collaboration tool for assessing risk of bias.
MAIN RESULTS
Ten studies (813 participants) met the inclusion criteria. Two studies only included participants 18 years and younger; six studies only included participants 18 years and older; one study included participants between 16 and 65 years of age and one study included only adults but did not specify the age range. Eight of the included studies had a high risk of bias. The included studies were clinically heterogeneous. We undertook no meta-analysis.The primary outcome measures of this review were: adverse effects (as defined by the study authors) and participant satisfaction (as defined by the study authors). In one study comparing propofol/fentanyl with ketamine/midazolam, delayed adverse reactions (nightmares and behavioural change) were noted in 10% of the ketamine/midazolam group and none in the propofol/fentanyl group. Seven individual studies reported no evidence of a difference in adverse effects between intravenous propofol, with and without adjunctive analgesic agents, and alternative interventions. Three individual studies reported no evidence of a difference in pain at the injection site between intravenous propofol and alternative interventions. Four individual studies reported no evidence of a difference in participant satisfaction between intravenous propofol, with and without adjunctive analgesic agents, and alternative interventions (ketamine, etomidate, midazolam). All the studies employed propofol without the use of an adjunctive analgesic and all, except one, were small (fewer than 100 participants) studies. The quality of evidence for the adverse effects and participant satisfaction outcomes was very low.Nine included studies (eight comparisons) reported all the secondary outcome measures of the review except mortality. It was not possible to pool the results of the included studies for any of the secondary outcome measures because the comparator interventions were different and the measures were reported in different ways. Seven individual studies reported no evidence of difference in incidence of hypoxia between intravenous propofol, with and without adjunctive analgesic agents, and alternative interventions.
AUTHORS' CONCLUSIONS
No firm conclusions can be drawn concerning the comparative effects of administering intravenous propofol, with or without an adjunctive analgesic agent, with alternative interventions in participants undergoing PS in the ED setting on adverse effects (including pain at the injection site) and participant satisfaction. The review was limited because no two included studies employed the same comparator interventions, and because the number of participants in eight of the included studies were small (fewer than 100 participants).
Topics: Adolescent; Adult; Anesthesia; Anesthetics, Intravenous; Emergency Service, Hospital; Etomidate; Fentanyl; Humans; Ketamine; Midazolam; Middle Aged; Propofol; Randomized Controlled Trials as Topic
PubMed: 26222247
DOI: 10.1002/14651858.CD007399.pub2 -
Journal of Medicine and Life Jan 2024This study aimed to identify novel Glyoxalase-I (Glo-I) inhibitors with potential anticancer properties, focusing on anthraquinone amide-based derivatives. We...
This study aimed to identify novel Glyoxalase-I (Glo-I) inhibitors with potential anticancer properties, focusing on anthraquinone amide-based derivatives. We synthesized a series of these derivatives and conducted in silico docking studies to predict their binding interactions with Glo-I. In vitro assessments were performed to evaluate the anti-Glo-I activity of the synthesized compounds. A comprehensive structure-activity relationship (SAR) analysis identified key features responsible for specific binding affinities of anthraquinone amide-based derivatives to Glo-I. Additionally, a 100 ns molecular dynamics simulation assessed the stability of the most potent compound compared to a co-crystallized ligand. Compound MQ3 demonstrated a remarkable inhibitory effect against Glo-I, with an IC concentration of 1.45 µM. The inhibitory potency of MQ3 may be attributed to the catechol ring, amide functional group, and anthraquinone moiety, collectively contributing to a strong binding affinity with Glo-I. Anthraquinone amide-based derivatives exhibit substantial potential as Glo-I inhibitors with prospective anticancer activity. The exceptional inhibitory efficacy of compound MQ3 indicates its potential as an effective anticancer agent. These findings underscore the significance of anthraquinone amide-based derivatives as a novel class of compounds for cancer therapy, supporting further research and advancements in targeting the Glo-I enzyme to combat cancer.
Topics: Humans; Amides; Anthraquinones; Antineoplastic Agents; Enzyme Inhibitors; Lactoylglutathione Lyase; Molecular Docking Simulation; Molecular Dynamics Simulation; Structure-Activity Relationship
PubMed: 38737655
DOI: 10.25122/jml-2023-0257