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1.
Chembiochem ; 25(4): e202300786, 2024 02 16.
Article in English | MEDLINE | ID: mdl-38126970

ABSTRACT

The allylic trans-cyclooctene (TCO) functionality facilitates powerful control over the spatiotemporal activity of bio-active molecules, enabling precision targeting of druglike and imaging modalities. However, the introduction of this function onto molecules remains chemically challenging, particularly for peptides. Modification with TCOs of this important class of biomolecules remains a challenge, primarily due to the sensitivity of the TCO group to the strong acids typically used in global deprotection during solid phase peptide synthesis. Here, we present a novel synthetic approach to site-selectively introduce TCO-groups in peptides. Our approach utilizes azide groups to mask amine functions, enabling selective introduction of the TCO on a single lysine residue. Staudinger reduction of the azides back to the corresponding amines proceeds without disturbing the sensitive TCO. We show that using our method, we can produce TCO-inactivated antigenic peptides of previously unseen complexity.


Subject(s)
Carbamates , Lysine , Cyclooctanes/chemistry , Peptides/chemistry , Azides/chemistry , Amines
2.
Rev Sci Instrum ; 92(4): 045006, 2021 Apr 01.
Article in English | MEDLINE | ID: mdl-34243376

ABSTRACT

A dielectric AC magnetic sensor in layered ferrites/piezoelectric composites was fabricated and developed, whereby its high magnetodielectric (MDE) effects, the typical magnetic-sensing parameters, were systematically characterized at zero bias. Polycrystalline ferrites were synthesized by the solid-state sintering technique with a composition of Ni0.7Zn0.3Tb0.02Fe1.98O4, and the desired spinel structure and soft magnetic properties were confirmed by x-ray diffraction and VSM, respectively. The field-induced charge order insulating state in piezoelectric ceramics accounts for the suppressed permittivity, which enables the possibility of a highly sensitive magnetic sensor at zero bias field. Experimental results exhibit that a small variation in H as low as 100 mOe can be clearly distinguished with a favorable nonlinearity of 2.24%. Meanwhile, the output stability of the presented sensor under 2h of constant and continuous excitation was tested within a favorable fluctuating tolerance range of 6.14-6.28 nF, and the estimated uncertainty of ∼0.063 038 nF was verified by statistical analysis. The presented ferrite/piezoelectric magnetic sensors exhibiting a high MDE response without the requirement for an external magnetic bias are of importance for use in bio-magnetic field detection due to metrics of miniaturization, high sensitivity, and favorable stabilities.

3.
Sci Rep ; 10(1): 20170, 2020 Nov 19.
Article in English | MEDLINE | ID: mdl-33214584

ABSTRACT

This report is on studies directed at the nature of magneto-electric (ME) coupling by ferromagnetic resonance (FMR) under an electric field in a coaxial nanofiber of nickel ferrite (NFO) and lead zirconate titanate (PZT). Fibers with ferrite cores and PZT shells were prepared by electrospinning. The core-shell structure of annealed fibers was confirmed by electron- and scanning probe microscopy. For studies on converse ME effects, i.e., the magnetic response of the fibers to an applied electric field, FMR measurements were done on a single fiber with a near-field scanning microwave microscope (NSMM) at 5-10 GHz by obtaining profiles of both amplitude and phase of the complex scattering parameter S11 as a function of bias magnetic field. The strength of the voltage-ME coupling Av was determined from the shift in the resonance field Hr for bias voltage of V = 0-7 V applied to the fiber. The coefficient Av for the NFO core/PZT shell structure was estimated to be - 1.92 kA/Vm (- 24 Oe/V). A model was developed for the converse ME effects in the fibers and the theoretical estimates are in good agreement with the data.

4.
Phys Chem Chem Phys ; 21(45): 25187-25195, 2019 Dec 07.
Article in English | MEDLINE | ID: mdl-31696167

ABSTRACT

Amyloid oligomers are suspected as toxic agents in neurodegenerative disease, and are transient and often heterogeneous, making them difficult to detect. Here we show an approach to track the development of amyloid oligomers in situ by room temperature, continuous wave (cw) 9 and 95 GHz EPR. Three amyloid peptides with the 2,2,6,6-tetramethyl-N-oxyl-4-amino-4-carboxylic acid (TOAC) spin label were synthesized by solid phase peptide synthesis: T0EZ (TKVKVLGDVIEVGG) with TOAC (T) at the N-terminus, T5EZ with TOAC in the middle (KVKVTGDVIEVG) and T12EZ with TOAC at the C-terminus (KVKVLGDVIEVTG). These sequences are derived from the K11V (KVKVLGDVIEV) amyloid peptide, which self-aggregates to oligomers with a ß-sheet configuration (A. Laganowsky, et al., Science, 2012, 335, 1228-1231). To monitor oligomerization, the rotational correlation time (τr) is measured by cw-EPR. For the backbone-fixed TOAC label that is devoid of local mobility τr should reflect the rotation and thereby the size of the peptide, resp. oligomer. For T5EZ a good match between the measured τr and the size of the peptide is obtained, showing the validity of the approach. One of the three peptides (T0EZ) aggregates (circular dichroism), whereas the other two do not. Since also the respective MTSL (S-(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)methyl methanesulfonothioate) labelled peptides fail to aggregate, molecular crowding due to the label, rather than the helix-inducing properties of TOAC, seems to be responsible. Following in situ oligomer formation of T0EZ by the change in rotational correlation time, two oligomers are observed, a 5-6 mer and a 15-18 mer. The EPR approach, particularly 95 GHz EPR, enables following oligomerization of one monomer at a time, suggesting that the cw-EPR approach presented is a novel tool to follow amyloid oligomerization with high resolution.


Subject(s)
Amino Acids/chemistry , Amyloid beta-Peptides/chemistry , Peptides/chemistry , Spin Labels , Cyclic N-Oxides/chemistry , Electron Spin Resonance Spectroscopy , Models, Molecular , Molecular Structure , Peptides/chemical synthesis
5.
Rev Sci Instrum ; 90(1): 015004, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30709188

ABSTRACT

A high-Q magnetoelectric (ME) gyrator consisting of a trilayer laminate of nickel-iron-based constant elasticity alloy (Ni-Fe-Cr) and lead zirconate titanate with a coil wound around it has been developed and systematically characterized. Highly efficient magneto-mechanical-electric conversion can be achieved by means of the combination contributions of high quality factors from individuals, and much energy can be transferred through the gyration device. Under an electromechanical resonance frequency of 54.04 kHz, experimental results show that maximum efficiency reaches as high as 88.5% under an extremely low input density of 3.31 µW/cm3 with an optimum load resistance of 9.6 kΩ and a magnetic bias of 66 Oe. Such a highly efficient ME gyrator with a high Q factor can be beneficial or degrade the design goals that are likely to be achievable for practical applications in compact power transfer electronic devices.

6.
Vestn Khir Im I I Grek ; 175(4): 59-61, 2016.
Article in English, Russian | MEDLINE | ID: mdl-30457273

ABSTRACT

Antireflux resection of mucous membrane of esophagogastric anastomosis (ARMS) was performed on 6 patients with typical symptoms of gastroesophageal reflux disease (GERD). The patients had a short segment of сolumnar-celled metaplasia (1-2 cm) without radiological and endoscopic signs of hiatal hernia. All the patients received medicamentous therapy by antisecretory agents more than 3 years. The operation included the endoscopic resection of2/3 circle of mucous membrane of esophagogastric anastomosis and resection of the area of columnar-celled metaplasia. The results of treatment were assessed during 3-7 months after ARMS. There was noted an absence of clinical manifestations of GERD, regression of inflammatory signs of mucous coat of esophagus in 4 out of 6 patients. Symptoms of GERD remained in 2 patients, although the intensity of signs significantly decreased.


Subject(s)
Barrett Esophagus , Endoscopic Mucosal Resection/methods , Esophagogastric Junction , Gastroesophageal Reflux/complications , Adolescent , Adult , Barrett Esophagus/diagnosis , Barrett Esophagus/etiology , Barrett Esophagus/surgery , Esophagogastric Junction/diagnostic imaging , Esophagogastric Junction/pathology , Esophagogastric Junction/surgery , Esophagoscopy/methods , Female , Gastroesophageal Reflux/diagnosis , Humans , Male , Metaplasia , Middle Aged , Treatment Outcome
7.
Carbohydr Res ; 356: 142-51, 2012 Jul 15.
Article in English | MEDLINE | ID: mdl-22429772

ABSTRACT

We here describe the synthesis of glucosylated teichoic acid (TA) fragments using two complementary fluorous scaffolds. The use of a perfluorooctylpropylsulfonylethyl (F-Pse) linker in combination with (glucosyl)glycerol phosphoramidite building blocks allows for the assembly of TA fragments with a terminal phosphate mono-ester, whereas the use of a perfluorooctylsuccinyl spacer delivers TA oligomers featuring a terminal alcohol functionality. These complementary linker systems have been developed because the nature of the TA chain terminus can play a role in the biological activity of the synthetic TAs. A novel α-glucosylated glycerolphosphoramidite building block is introduced to allow for a robust light fluorous synthetic protocol.


Subject(s)
Enterococcus faecalis/chemistry , Hydrocarbons, Fluorinated/chemistry , Teichoic Acids/chemical synthesis , Cell Wall/chemistry , Glycosylation , Molecular Structure , Organophosphorus Compounds/chemistry
8.
Kardiologiia ; 51(2): 40-4, 2011.
Article in Russian | MEDLINE | ID: mdl-21627597

ABSTRACT

Clinicostatistical analysis of arterial hypertension complicated with hypertensive crisis using data of Moscow A.S.Puchkov Station of Urgent and Emergent Medical Aid revealed 14% rise in number of hypertensive crises during the period from 2005 to 2009. Number of hypertensive crises increased among persons of young age (18-35 years). Frequency of cerebrovascular complications of hypertensive crises was age dependent with maximal values among men aged 36-74 years and women older than 75 years.


Subject(s)
Hypertension/epidemiology , Adolescent , Adult , Age Distribution , Aged , Data Interpretation, Statistical , Disease Progression , Female , Follow-Up Studies , Humans , Hypertension/physiopathology , Male , Middle Aged , Morbidity/trends , Moscow/epidemiology , Retrospective Studies , Risk Factors , Sex Distribution , Young Adult
9.
Kardiologiia ; 50(10): 39-43, 2010.
Article in Russian | MEDLINE | ID: mdl-21118178

ABSTRACT

Butylaminohydroxypropoxyphenoxymethyl methyloxadiazole was used in prehospital treatment of 40 patients (15 women, 25 men aged 63+/-17.1 years) with complicated hypertensive crises (HC) characterized by acute involvement or high risk of progression of damage of internal organs. The drug was administered as intravenous bolus injection of 10-50 mg (1-5 ml of 1% solution) under control of arterial pressure (AP) and heart rate (HR). The patients noted alleviation of symptoms by 15th min and disappearance of main manifestations of HC by 30th min. Systolic and diastolic AP were significantly lowered from baseline 190.0+/-24.4 and 105.0+/-13.5 mm Hg to 153.3+/-20,1 and 85.0+/-12,6 mm Hg, respectively. Mean dynamics of lowering of systolic and diastolic AP was 19.5 and 19%, respectively. This was accompanied by 15.4% lowering of HR (from 90.3+/-12.0 to 76.4+/-9.4 bpm). Myocardial ischemia in those patients who had it diminished or disappeared. Thus in patients with complicated HC the study drug exerted effective antihypertensive and antiischemic actions. It was well tolerated and did not cause significant side effects.


Subject(s)
Blood Pressure/drug effects , Heart Rate/drug effects , Hypertension, Malignant/drug therapy , Oxadiazoles , Acute Coronary Syndrome/etiology , Acute Disease , Adrenergic alpha-1 Receptor Antagonists/administration & dosage , Adrenergic alpha-1 Receptor Antagonists/adverse effects , Adrenergic beta-Antagonists/administration & dosage , Adrenergic beta-Antagonists/adverse effects , Aged , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/adverse effects , Drug Repositioning , Emergency Medical Services/methods , Emergency Medical Services/organization & administration , Female , Humans , Hypertension, Malignant/complications , Hypertension, Malignant/physiopathology , Hypertensive Encephalopathy/etiology , Injections, Intravenous , Male , Middle Aged , Oxadiazoles/administration & dosage , Oxadiazoles/adverse effects , Therapies, Investigational
10.
Vestn Khir Im I I Grek ; 169(3): 57-9, 2010.
Article in Russian | MEDLINE | ID: mdl-20804027

ABSTRACT

Fecal incontinence in children after surgical correction of anorectal defects and trauma of the holding apparatus of the rectum in certain cases can be dependent on low basal pressure in the anal canal at the expense of incompetence of the interior sphincter muscle of the anus. In order to eliminate low pressure in the anal canal we introduced polyacrylamide gel "DAM +" into its submucous layer. The introduction of this volume-forming substance into the anal canal was an effective procedure. Fecal incontinence became less in all cases, and completely regressed in 50% of the patients.


Subject(s)
Acrylic Resins/therapeutic use , Anal Canal/surgery , Fecal Incontinence/surgery , Adolescent , Animals , Child , Child, Preschool , Humans , Manometry , Pressure , Rats , Rats, Wistar , Treatment Outcome
11.
Vestn Khir Im I I Grek ; 169(1): 85-8, 2010.
Article in Russian | MEDLINE | ID: mdl-20387614

ABSTRACT

An analysis of treatment of 75 children of the age from 3 years to 17 admitted to the St. Petersburg Pediatric Medical Academy was made. All the children were admitted with the diagnoses of blunt (closed) injuries of the abdomen, ruptures of the spleen, intra-abdominal bleedings. The patients were divided into 3 groups according to the periods of hospitalization. In each group the patients were examined and treated which corresponded to the surgical strategy for rupture of the spleen at that period. Different methods of examinations and therapy were determined in the three groups of patients with similar pathology.


Subject(s)
Abdominal Injuries/diagnosis , Diagnostic Imaging/methods , Laparotomy/methods , Spleen/injuries , Splenectomy/methods , Wounds, Nonpenetrating/diagnosis , Abdominal Injuries/complications , Abdominal Injuries/surgery , Adolescent , Child , Child, Preschool , Diagnosis, Differential , Female , Follow-Up Studies , Hemoperitoneum/diagnosis , Hemoperitoneum/etiology , Hemoperitoneum/surgery , Humans , Male , Retrospective Studies , Rupture , Trauma Severity Indices , Treatment Outcome , Wounds, Nonpenetrating/complications , Wounds, Nonpenetrating/surgery
12.
Appl Magn Reson ; 36(2-4): 209-222, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19946595

ABSTRACT

Plaques containing the aggregated beta-Amyloid (Abeta) peptide in the brain are the main indicators of Alzheimer's disease. Fibrils, the building blocks of plaques, can also be produced in vitro and consist of a regular arrangement of the peptide. The initial steps of fibril formation are not well understood and could involve smaller aggregates (oligomers) of Abeta. Such oligomers have even been implicated as the toxic agents. Here, a method to study oligomers on the time scale of aggregation is suggested. We have labeled the 40 residue Abeta peptide variant containing an N-terminal cysteine (cys-Abeta) with the MTSL [1-oxyl-2,2,5,5-tetramethyl-Delta-pyrroline-3-methyl] methanethiosulfonate spin label (SL-Abeta). Fibril formation in solutions of pure SL-Abeta and of SL-Abeta mixed with Abeta was shown by Congo-red binding and electron microscopy. Continuous-wave 9 GHz electron paramagnetic resonance reveals three fractions of different spin-label mobility: one attributed to monomeric Abeta, one to a multimer (8-15 monomers), and the last one to larger aggregates or fibrils. The approach, in principle, allows detection of oligomers on the time scale of aggregation.

13.
Vestn Khir Im I I Grek ; 166(3): 22-5, 2007.
Article in Russian | MEDLINE | ID: mdl-18050636

ABSTRACT

An analysis of results of surgical treatment of 28 patients with lung cancer who underwent resection of the left atrium has shown that squamous cell cancer was diagnosed in 18 patients (64%), adenocarcinoma--in 5 (18%), dimorphous cancer--in 2 (7%), mucoepidermoid cancer in 2 (7%), atypical carcinoid--in 1 patient (4%). The degree of regional lymphogenic spread of the tumor NO took place in 11 patients (39%), N1--in 6 patients (22%), N2--in 11(39%). True invasion of the tumor to the left atrium myocardium took place in 20 patients (71%), involvement of the pulmonary vein orifices in the tumor process--in 8 (29%). Resection of the atrium was made using mechanical suturing apparatuses. The right side resections were fulfilled in 16 patients (57%), left side resections in 12 patients (43%). Pneumonectomy was fulfilled in 26 patients (93%), lobectomy--in 2 patients (7%). The operative interventions in five cases (18%) were estimated as microscopically non-radical (R1). The average time in the intensive care unit after operation was 3 days (from 1 till 12), in the surgical thoracal department--18 days (from 13 till 37). In the early postoperative period one patient died (4%), complications were noted in 5 patients (18%). The total one year survival was 69%, three year survival--39%, 5 year survival--17%. The survival median was 23 months. Resection of the left atrium in the selected lung cancer patients was not followed by growing operative lethality and the acceptable long term results were obtained.


Subject(s)
Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/therapy , Heart Atria/surgery , Lung Neoplasms/epidemiology , Lung Neoplasms/therapy , Adult , Aged , Electrocardiography , Female , Humans , Male , Middle Aged , Neoplasm Invasiveness , Preoperative Care , Spirometry , Treatment Outcome
14.
J Pept Res ; 61(6): 298-306, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12753377

ABSTRACT

As part of a program towards the development of novel antibiotics, a convenient method for solid-phase synthesis of the cyclic cationic peptide polymyxin B1 and analogues thereof is described. The methodology, based on cleavage-by-cyclization using Kenner's safety-catch linker, yields crude products with purities ranging from 37-67%. Antibacterial assays revealed that analogues 23-26, in which the (S)-6-methyloctanoic acid moiety is replaced with shorter acyl chains, exhibit distinct antimicrobial activity. The results suggest that the length of the acyl chain is rather critical for antimicrobial activity. On the other hand, substitution of the hydrophobic ring-segment D-Phe-6/Leu-7 in polymyxin B1 with dipeptide mimics (i.e. analogues 27-33) resulted in almost complete loss of antimicrobial activity.


Subject(s)
Polymyxins/analogs & derivatives , Polymyxins/chemical synthesis , Bacillus/drug effects , Chromatography, High Pressure Liquid , Microbial Sensitivity Tests , Molecular Structure , Polymyxins/chemistry , Polymyxins/pharmacology , Structure-Activity Relationship
15.
FEBS Lett ; 537(1-3): 6-10, 2003 Feb 27.
Article in English | MEDLINE | ID: mdl-12606022

ABSTRACT

Extracellular matrix (ECM) of tissues, vascular tissue in particular, contains a high concentration of negatively charged glycosaminoglycans (GAGs), which are involved in the regulation of cell motility, cell proliferation and the regulation of enzyme activities. Previously, we have shown that the vascular ECM is capable of binding an extremely high concentration of positively charged molecules, such as polylysine. Vascular ECM can be used therefore as a substrate for binding and retention of drugs delivered intravascularly, if these drugs are endowed with an ability to bind to the vascular ECM. In this study, we evaluated a number of positively charged molecules as potential affinity vehicles for delivery of drugs to the vascular ECM. We labelled the molecules of interest with fluorescence and compared them ex vivo in terms of binding and retention in the de-endothelialised rat carotid artery after intravascular delivery under pressure. High molecular weight polylysine (84 kDa) and polyamidoamine (PAMAM) dendrimers accumulated in the wall of the artery up to a concentration of 10 mg/ml and were not washed away significantly after 4 h of perfusion of the artery. A 24-mer peptide containing a consensus sequence for binding to GAGs (ARRRAARA)(3), 2.7 kDa, was comparable to high molecular weight polylysine and dendrimers in terms of binding and retention. A 14-mer GAG-binding peptide from vitronectin and low molecular weight polylysine, 3 kDa, accumulated in the vascular wall up to about 3 mg/ml and was washed away after 30 min of perfusion. A 10-mer consensus GAG-binding peptide did not bind significantly to the vascular tissue. We conclude that the consensus 24-mer GAG-binding peptide is by far superior to polylysine of a similar molecular weight in terms of binding to vascular tissue, and can provide high accumulation and long-term retention of a low molecular weight compound (fluorescein, as a model molecule) in the vascular wall. Rationally designed GAG-binding peptides can be useful as affinity vehicles for targeting drugs to the vascular ECM.


Subject(s)
Carotid Arteries/metabolism , Muscle, Smooth, Vascular/metabolism , Oligopeptides/chemistry , Polylysine/chemistry , Amino Acid Sequence , Animals , Biological Transport , Fluorescent Dyes , In Vitro Techniques , Kinetics , Oligopeptides/pharmacokinetics , Polylysine/pharmacokinetics , Rats
16.
J Biomol NMR ; 20(4): 325-31, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11563556

ABSTRACT

Resonance assignments recently obtained on immobilized polypeptides and a membrane protein aggregate under Magic Angle Spinning are compared to random coil values in the liquid state. The resulting chemical shift differences (secondary chemical shifts) are evaluated in light of the backbone torsion angle psi previously reported using X-ray crystallography. In all cases, a remarkable correlation is found suggesting that the concept of secondary chemical shifts, well established in the liquid state, can be of similar importance in the context of multiple-labelled polypeptides studied under MAS conditions.


Subject(s)
Nuclear Magnetic Resonance, Biomolecular/methods , Peptides/chemistry , Proteins/chemistry , Carbon/chemistry , Protein Structure, Secondary
17.
Nature ; 393(6682): 280-4, 1998 May 21.
Article in English | MEDLINE | ID: mdl-9607767

ABSTRACT

A small protein, VPg, is covalently linked to the 5' end of the plus-stranded poliovirus genomic RNA. Poliovirus messenger RNA, identical in nucleotide sequence to genomic RNA, is not capped at its 5' end by the methylated structure that is common to most eukaryotic mRNAs. These discoveries presented two problems. First, as cap structures are usually required for translation of mRNA into protein, how does this uncapped viral RNA act as a template for translation? Second, what is the function of VPg? The identification of the internal ribosomal-entry site, which allows the entry of ribosomes into viral mRNA independently of the 5' mRNA end, has solved the first conundrum. Here we describe the resolution of the second problem. VPg is linked to the genomic RNA through the 5'-terminal uridylic acid of the RNA. We show that VPg can be uridylylated by the poliovirus RNA polymerase 3Dpol. Uridylylated VPg can then prime the transcription of polyadenylate RNA by 3Dpol to produce VPg-linked poly(U). Initiation of transcription of the poliovirus genome from the polyadenylated 3' end therefore depends on VPg.


Subject(s)
DNA-Directed RNA Polymerases/metabolism , Poliovirus/genetics , RNA, Viral/biosynthesis , RNA-Dependent RNA Polymerase , Viral Core Proteins/metabolism , Amino Acid Sequence , DNA-Directed RNA Polymerases/genetics , DNA-Directed RNA Polymerases/isolation & purification , Escherichia coli , Molecular Sequence Data , Poliovirus/enzymology , Poly A/metabolism , Poly U/metabolism , Recombinant Proteins , Transcription, Genetic , Uridine/metabolism , Uridine Triphosphate/metabolism , Viral Core Proteins/chemical synthesis
18.
Mol Biol (Mosk) ; 27(1): 174-84, 1993.
Article in Russian | MEDLINE | ID: mdl-8483469

ABSTRACT

Acyclic analogs of thymidine, adenine, and cytosine where the ribose moiety is replaced with cis-5-hydroxypenthene, were obtained via condensation of cis-5-acetoxy-1-bromo-2-pentene with nucleic acid bases. Triphosphate derivatives of the new nucleosides were also synthesized to evaluate their action as terminators of DNA synthesis catalyzed by DNA polymerases.


Subject(s)
Nucleosides/chemical synthesis , Catalysis , DNA/biosynthesis , DNA-Directed DNA Polymerase/chemistry , Nucleic Acids/chemistry , Nucleosides/chemistry , Terminator Regions, Genetic
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