The specificity of vesicular transport is regulated, in part, by the interaction of a vesicle-associated membrane protein termed synaptobrevin/VAMP with a target compartment membrane protein termed ...syntaxin. These proteins, together with SNAP-25 (synaptosome-associated protein of 25 kDa), form a complex which serves as a binding site for the general membrane fusion machinery. Synaptobrevin/VAMP and syntaxin are ubiquitously expressed proteins and are believed to be involved in vesicular transport in most (if not all) cells. However, SNAP-25 is present almost exclusively in the brain, suggesting that a ubiquitously expressed homolog of SNAP-25 exists to facilitate transport vesicle/target membrane fusion in other tissues. Using the yeast two-hybrid system, we have identified a 23-kDa protein from human B lymphocytes (termed SNAP-23) that binds tightly to multiple syntaxins and synaptobrevins/VAMPs in vitro. SNAP-23 is 59% identical with SNAP-25. Unlike SNAP-25, SNAP-23 was expressed in all tissues examined. These findings suggest that SNAP-23 is an essential component of the high affinity receptor for the general membrane fusion machinery and an important regulator of transport vesicle docking and fusion in all mammalian cells.
Objectives: The present study aimed to establish significant and validated quantitative structure-activity relationship (QSAR) models for neuraminidase inhibitors and correlate their physicochemical, ...steric, and electrostatic properties with their anti-influenza activity. Materials and Methods: We have developed and validated 2D and 3D QSAR models by using multiple linear regression, partial least square regression, and k-nearest neighbor-molecular field analysis methods. Results: 2D QSAR models had q.sup.2: 0.950 and pred_r.sup.2: 0.877 and 3D QSAR models had q.sup.2: 0.899 and pred_r.sup.2: 0.957. These results showed that the models werere predictive. Conclusion: Parameters such as hydrogen count and hydrophilicity were involved in 2D QSAR models. The 3D QSAR study revealed that steric and hydrophobic descriptors were negatively contributed to neuraminidase inhibitory activity. The results of this study could be used as platform for design of better anti-influenza drugs. Key words: QSAR, neuraminidase inhibitors, thiazolidine-4-carboxylic acid derivatives, anti-influenza activity Amac: Bu calisma noraminidaz inhibitorlerinin belirgin ve valide nicel yapi-aktivite iliskisi (QSAR) modellerini kurmayi ve bu bilesiklerin fizikokimyasal, sterik ve elektrostatik ozelliklerini anti-influenza aktiviteleriyle korele etmeyi amaclamistir. Gerec ve Yontemler: Coklu regresyon, parsiyel en dusuk kare regresyon ve k-en yakin komsu molekuler alan analizi yontemlerini kullanarak 2D ve 3D QSAR modellerini gelistirdik ve valide ettik. Bulgular: Gelistirilen 2D QSAR modeli icin q.sup.2: 0,950 ve pred_r.sup.2: 0,877 bulunurken, 3D QSAR modeli icin q.sup.2: 0,899 ve pred_r.sup.2: 0,957 bulundu. Bu sonuclar modellerinin tahmin gucunun oldugunu gosterdi. Sonuc: Hidrojen sayisi ve hisrofilisite gibi parametreler 2D QSAR modellerine dahil edildi. 3D QSAR modelleri sterik ve hisrofobik tanimlayicilarin noraminidaz inhibitor aktivitesine negatif etki ettigi belirlendi. Bu calismanin sonuclari influenzaya karsi ilac tasarlamak icin bir platform olarak kullanilabilir. Anahtar kelimeler: QSAR, noraminidaz inhibitorleri, tiyazolidin-4-karboksilik asit deriveleri, anti-influenza aktivitesi
Thiazolidinone is considered as a biologically important active scaffold that possesses almost all types of biological activities. Successful introduction of ralitoline as a potent anti-convulsant, ...etozoline as a antihypertensive, pioglitazone as a hypoglycemic agent and thiazolidomycin activity against streptomyces species proved potential of thiazolidinone moiety. This diversity in the biological response profile has attracted the attention of many researchers to explore this skeleton to its multiple potential against several activities. This review is complementary to earlier reviews and aims to review the work reported on various biological activities of thiazolidinone derivatives from year 2000 to the beginning of 2011. Data are presented for active compounds, some of which have passed the preclinical testing stage.
A significant advancement in the field of epigenetic drug discovery has been evidenced in recent years. Epigenetic alterations are hereditary, nevertheless reversible variations to DNA or histone ...adaptations that regulate gene function individualistically of the fundamental sequence. The design and synthesis of various drugs targeting epigenetic regulators open a new door for epigenetic-targeted therapies to parade worthwhile therapeutic potential for haematological and solid malignancies. Several ongoing clinical trials on dual targeting strategy are being conducted comprising HDAC inhibitory component and an epigenetic regulating agent. In this perspective, the review discusses the pharmacological aspects of HDAC and other epigenetic regulating factors as dual inhibitors as an emerging alternative approach for combination therapies.
Currently, cervical cancer (CC) is the fourth recorded widespread cancer among women globally. There are still many cases of metastatic or recurring disease discovered, despite the incidence and ...fatality rates declining due to screening identification and innovative treatment approaches. Palliative chemotherapy continues to be the standard of care for patients who are not contenders for curative therapies like surgery and radiotherapy. This article seeks to provide a thorough and current summary of therapies that have been looked into for the management of CC. The authors emphasize the ongoing trials while reviewing the findings of clinical research. Agents that use biological mechanisms to target different molecular pathways such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), poly ADP-ribosepolymerase (PARP), and epigenetic biological mechanisms epitomize and offer intriguing research prospects.Currently, cervical cancer (CC) is the fourth recorded widespread cancer among women globally. There are still many cases of metastatic or recurring disease discovered, despite the incidence and fatality rates declining due to screening identification and innovative treatment approaches. Palliative chemotherapy continues to be the standard of care for patients who are not contenders for curative therapies like surgery and radiotherapy. This article seeks to provide a thorough and current summary of therapies that have been looked into for the management of CC. The authors emphasize the ongoing trials while reviewing the findings of clinical research. Agents that use biological mechanisms to target different molecular pathways such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), poly ADP-ribosepolymerase (PARP), and epigenetic biological mechanisms epitomize and offer intriguing research prospects.
The main objective of the present study was to establish significant and validated QSAR models for imidazoles and sulfonamides to explore the relationship between their physicochemical properties and ...antidiabetic activity. Two dimensional QSAR models had been developed by multiple linear regression and partial least square analysis methods, and then validated for internal and external predictions. The established 2D QSAR models were statistically significant and highly predictive. The validation methods provided significant statistical parameters with q2 > 0.5 and pred_r2 > 0.6, which proved the predictive power of the models. The developed 2D QSAR models revealed the significance of SlogP and T_N_O_5, and Mol.Wt and SsBrE-index properties of imidazoles and sulfonamides on their antidiabetic activity, respectively. These results should prove to be an essential guide for the further design and development of new imidazoles and sulfonamides having better antidiabetic activity.
There is an increasing commercial demand for nanoparticles due to their wide applicability in various areas such as electronics, catalysis, chemistry, energy and medicine. Metallic nanoparticles are ...traditionally synthesized by wet chemical techniques, where the chemicals used are quite often toxic and flammable. In this research article we present a simple and eco-friendly biosynthesis of silver nanoparticles using Garcinia mangostana leaf extract as reducing agent. The aqueous silver ions when exposed to leaf extract were reduced and resulted in silver nanoparticles whose average size was 35nm. The silver nanoparticles were characterized by UV–Visible, Fourier transform infra-red spectroscopy (FT-IR) and transmission electron microscopy (TEM) techniques. Furthermore these biologically synthesized nanoparticles were found to be highly effective against different multi-drug resistant human pathogens.
Xenotropic Murine Leukemia Virus-related (XMRV) virus is a recently identified mouse gammaretrovirus that has the ability to infect certain human cells. In this study, we investigated the ...susceptibility of primary neuronal cell types to infection with XMRV.
We observed that the human primary progenitors, progenitor-derived neurons, and progenitor-derived astrocytes supported XMRV multiplication. Interestingly, both progenitors and progenitor-derived neurons were more susceptible compared with progenitor-derived astrocytes. In addition, XMRV-infected Jurkat cells were able to transmit infection to neuronal cells.
These data suggest that neuronal cells are susceptible for XMRV infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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