Wyniki wyszukiwania - Biblioteka Nauki

1

Design of small molecule inhibitors of type III secretion system ATPase EscN from enteropathogenic Escherichia coli

100%

Bzdzion L. , Krezel H. , Wrzeszcz K. , Grzegorek I. , Nowinska K. , Chodaczek G. , Swietnicki W.

Acta Biochimica Polonica

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2017

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tom 64

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nr 1

49-63

EN

Enteropathogenic E. coli (EPEC) is a human pathogen using type III secretion system for delivery of proteins directly into the human host. The system contains a single ATPase, EscN, which is essential for uncoupling of proteins from their complexes with chaperones before the delivery. The structure of EscN ATPase (PDB code: 2obm) was used to screen computationally for small molecule inhibitors blocking its active site. Two lead candidates were examined but only one, Compound 54, was selected for further optimization. After extended QSAR optimization, two derivatives were found to be competitive inhibitors of EscN capable of blocking ATPase activity with a Ki below 50 µM. One candidate, WEN05-03, with a Ki=16±2 µM, was also minimally toxic to mammalian cells as determined by other assays. In the cell infection model of HeLa cells with EPEC, Compound WEN05-03 completely blocked actin cluster formation at 100 µM concentration, when analyzed by confocal microscopy. The second best inhibitor of EscN ATPase activity was WEN04-34 with a Ki=46±2 µM. However, the compound was highly toxic to the BALB/3T3 cell line. In summary, the work identifies a compound blocking bacterial ATPase in its active site without causing cellular toxicity to the host cells. It is the first report showing feasibility of using bacterial virulence system ATPase as a target for safe, non-toxic compounds and offering a proof-of-concept for non-antibiotic alternatives.

2

Navigating cross-kinase selectivity space

100%

Aronov A. M. , McClain B. , Caron P. R. , Murcko M. A.

Cellular and Molecular Biology Letters

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2005

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tom 10

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nr Suppl.2

3

Target flexibility in molecular recognition

88%

McCammon J. A.

Cellular and Molecular Biology Letters

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2005

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tom 10

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nr Suppl.2

4

Substrate and inhibitor recognition of protein kinases: what in known about the catalytic subunit of phosphorylase kinase?

88%

Graves D. J. , Bartleson C. , Biorn A. , Pete M.

Cellular and Molecular Biology Letters

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1998

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tom 03

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nr 3

5

Enhanced microdialysis of neuropeptides

88%

Pettersson A. , Markides K. , Bergquist J.

Acta Biochimica Polonica

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2001

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tom 48

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nr 4

EN

An enhanced microdialysis method for neuropeptides is described and some preliminary results of this novel approach are presented. The enhancement is achieved by adding a vehicle (solid support) to the perfusion fluid in order to increase the diffusion coefficient across the membrane and efficiently transport the analytes towards the detector. The microdialysis samples are desalted and then analyzed on an electrospray ionization orthogonal time-of-flight mass spectrometer. The preliminary results show major increase in signal when comparing this new approach of microdialysis with ordinary microdialysis.

6

Scanning the proteome for targets of kinase inhibitors using bi-functional receptor ligands

75%

Kley N.

Cellular and Molecular Biology Letters

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2005

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tom 10

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nr Suppl.2

7

Acetylation of methyl 5-amino-1H-[1,2,4]triazole-3-carboxylate

75%

Dzygiel A. , Masiukiewicz E. , Rzeszotarska B.

Acta Biochimica Polonica

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2001

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tom 48

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nr 4

EN

Acetylation with acetic anhydride of methyl 5-amino-1ff-[1,2,4]triazole-3-carboxy- late, one of the hetareneamino acids, was studied using HPLC, H NMR, FTIR and GC-MS. The compound has a significantly decreased susceptibility to acetylation compared to 5-amino-1ff-[1,2,4]triazole itself. Two isomeric diacetylated products were found.

8

Novel small molecule inhibitors of c-terminal Src kinase [Csk]

75%

Kilimnik A. , Kostjukova M. N. , Pyatkin I. H. , Pronin A. M. , Strelnikowa S. R. , Fedotov Y. A. , Kolesnikov A. V.

Cellular and Molecular Biology Letters

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2003

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tom 08

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nr 2A

9

Nowe celowane leki małocząsteczkowe w leczeniu astmy

63%

Romantowski J. , Niedoszytko M. N.

Alergia Astma Immunologia - przegląd kliniczny

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2019

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tom 24

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nr 3

131-136

EN

Asthma is a common chronic bronchial disease that is a major social problem in the world. Despite significant advances in inhalation therapy in recent decades, severe asthma remains a challenge for modern medicine. The heterogeneity of the mechanisms behind the severity of symptoms and resistance to classic inhalation drugs significantly impedes the search for targeted drugs in a group of patients with no satisfactory disease control based on basic drugs. To date, research on new drugs in severe asthma has mainly focused on antibody synthesis. However, a relatively large molecule of these drugs imposes some restrictions on the way of their administration and diagostic targets. The article discusses new therapeutic options associated with low molecular weight drugs under 900 Dalton being developed in recent years

PL

Astma jest częstą chorobą przewlekła oskrzeli, stanowiącą istotny problem społeczny na świecie. Pomimo znacznego postępu w terapii wziewnej w ostatnich dekadach, astma ciężka stanowi nadal wyzwanie dla współczesnej medycyny. Heterogenność mechanizmów stojących za nasileniem objawów i oporność na klasyczne leki wziewne znacznie utrudnia poszukiwanie celowanych leków w grupie chorych nie uzyskujących zadowalającej kontroli choroby w oparciu o podstawowe leki. Dotychczasowe badania nad nowymi lekami w ciężkiej astmie koncentrują się głównie na syntezie przeciwciał. Jednak relatywnie duża cząsteczka tych leków nakłada na nie pewne ograniczenia związane z drogą podania i możliwymi punktami uchwytu. Niniejszy artykuł omawia nowe możliwości terapeutyczne związane z opracowywanymi w ostatnich latach lekami małocząsteczkowymi o masie poniżej 900 Daltonów.

10

Insights into selectivity of STI571 [GleevecTM] from X-ray crystallography

63%

Nowakowski J. , Sridhar V. , Thompson D. A. , Cronin C. N. , Vaughn D. E. , Gangloff A. R. , Sang B. C. , Zoa H. , Knuth M. W. , Swanson R. V. , Snell G. , Mol C. D. , Wilson K. P. , Mcree D. E.

Cellular and Molecular Biology Letters

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2003

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tom 08

|

nr 2A

11

The loading of human erythrocytes with small molecules by electroporation

63%

Saulis G.

Cellular and Molecular Biology Letters

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2005

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tom 10

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nr 1

12

Multiple molecular recognition mechanisms. Cytochrome P450 - a case study

63%

Wade R. C. , Motiejunas D. , Schleinkofer K. , Sudarko , Winn P. J. , Banerjee A.

Cellular and Molecular Biology Letters

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2005

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tom 10

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nr Suppl.2

13

Desorption-ionization on silicon for small molecules: a promising alternative to MALDI TOF

63%

Kraj A. , Dylag T. , Gorecka-Drzazga A. , Bargiel S. , Dziuban J. , Silberring J.

Acta Biochimica Polonica

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2003

|

tom 50

|

nr 3

EN

A method has been developed for laser desorption/ionization of catecholamines from porous silicon. This methodology is particularly attractive for analysis of small molecules. MALDI TOF mass spectrometry, although a very sensitive technique, utilizes matrices that need to be mixed with the sample prior to their analysis. Each matrix produces its own background, particularly in the low-molecular mass region. Therefore, detection and identification of molecules below 400 Da can be difficult. Desorption/ionization of samples deposited on porous silicon does not require addition of a matrix, thus, spectra in the low-molecular mass region can be clearly readable. Here, we describe a method for the analysis of catecholamines. While MALDI TOF is superior for proteomics/peptidomics, desorption/ionization from porous silicon can extend the operating range of a mass spectrometer for studies on metabo- lomics (small organic molecules and their metabolites, such as chemical neurotransmitters, prostaglandins, steroids, etc.).

14

Efficient characterization of kinase inhibitors using LeadCodeTM technology

63%

Degenhart C.

Cellular and Molecular Biology Letters

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2003

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tom 08

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nr 2A