Abstract：
:This review provides biochemical, analytical, and biological background information relating to beta-N-acetylhexosaminidase (HexNAc'ase; EC 3.2.1.52) as an emerging target for the design of low-molecular-weight antifungals. The article includes the following: (1) a biochemical description of HexNAc'ase (reaction catalyzed, nomenclature, and mechanism of action) that sets it apart from other, similar enzymes; (2) an overview and a critical evaluation of methods to assay the enzyme, including in crude extracts (photo- and fluorometric procedures with model substrates; HPLC/pulsed amperometric detection of N-acetylglucosamine and chito-oligomers; end-point vs. rate measurements); (3) a summary of some general characteristics of HexNAc'ases from fungi and organisms of other types (Km values, substrate preference, and glycoconjugation); (4) an hypothesis of a specific target function of wall-associated HexNAc'ase (a component of the assembly of surface-located enzymes effecting a continuous turnover and remodelling of the wall fabric through its combined hydrolytic and transglycosylating activities, and a mediator enzyme acting in concert with chitinase and chitin synthase to provide for the controlled lysis and synthesis of chitin during growth); (5) a tabulation of the structural formulae of reaction-based HexNAc'ase inhibitors with Ki values < or = 100 microM (some of them representing transition state mimics that could serve as leads for the development of new antifungals); and (6) an outline of approaches towards the establishment of a three-dimensional model of HexNAc'ase suitable for a truly rational design of antimycotics as well as agricultural fungicides.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Horsch M,Mayer C,Sennhauser U,Rast DMdoi
10.1016/s0163-7258(97)00110-1subject
Has Abstractpub_date
1997-10-01 00:00:00pages
187-218issue
1-3eissn
0163-7258issn
1879-016Xjournal_volume
76pub_type
杂志文章,评审abstract：:Neuropeptides are the largest class of intercellular signaling molecules, contributing to a wide variety of physiological processes. Neuropeptide receptors are therapeutic targets for a broad range of drugs, including medications to treat pain, addiction, sleep disorders, and nausea. In addition to >100 peptides with ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2017.11.006
更新日期：2018-05-01 00:00:00
abstract：:Thioredoxin 1 (Trx 1) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys- that is ubiquitously present in the human body. Trx 1 is a defensive protein induced by various stresses and has anti-oxidative, anti-apoptotic and anti-inflammatory effects. The anti-oxidative effect of Trx 1 is m...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2010.04.004
更新日期：2010-09-01 00:00:00
abstract：:Natural D-nucleosides are no longer the sole basis for designing effective antiviral analogues. Many antivirals with an opposite (L) configuration were reported, with lamivudine being the most notable example. In contrast, carbocyclic nucleoside analogues are significantly more enantioselective, and enantiomers with a...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(99)00062-5
更新日期：2000-03-01 00:00:00
abstract：:RSV infection of the lower respiratory tract in infants is the leading cause of pediatric hospitalizations and second to malaria in causing infant deaths worldwide. RSV also causes substantial morbidity in immunocompromised and elderly populations. The only available therapeutic is a prophylactic drug called Palivizum...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107712
更新日期：2020-10-27 00:00:00
abstract：:G-protein-coupled receptors (GPCRs) comprise the largest family of transmembrane receptors in the human genome that respond to a plethora of signals, including neurotransmitters, peptide hormones, and odorants, to name a few. They couple to second messenger signaling cascade mechanisms via heterotrimeric G-proteins. R...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(01)00160-7
更新日期：2001-11-01 00:00:00
abstract：:The developing lung is highly susceptible to damage from exposure to environmental toxicants particularly due to the protracted maturation of the respiratory system, extending from the embryonic phase of development in utero through to adolescence. The functional organization of the lungs requires a coordinated ontoge...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2007.01.011
更新日期：2007-05-01 00:00:00
abstract：:The "late sodium current" (I(NaL)) is a sustained component of the fast Na+ current of cardiac myocytes and neurons. As recently appreciated, common neurological and cardiac conditions are associated with abnormal I(NaL) enhancement, which may contribute to the pathogenesis of both electrical and contractile dysfuncti...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2008.06.001
更新日期：2008-09-01 00:00:00
abstract：:Hypertension is an epidemic health concern and a major risk factor for the development of cardiovascular disease. Although there are available treatment strategies for hypertension, numerous hypertensive patients do not have their clinical symptoms under control and it is imperative that new avenues to treat or preven...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2013.02.005
更新日期：2013-06-01 00:00:00
abstract：:Microsomal P450-mediated monooxygenase activity supported by NADPH requires an interaction between flavoprotein NADPH-cytochrome P450 reductase and cytochrome P450. These proteins have been identified as the simplest system (with the inclusion of a phospholipid (PL) component) that possesses monooxygenase function; ho...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(03)00031-7
更新日期：2003-05-01 00:00:00
abstract：:Cancer research has been focusing so far on genetic alterations in protein-coding genes. However, mounting evidence underlines the importance of epigenetic and post-transcriptional events in cancer progression and therapy resistance. Moreover, recent genome-wide studies show that disease-causing mutations and chromoso...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2018.04.001
更新日期：2018-09-01 00:00:00
abstract：:During the last decade, rigorous scientific methods have been applied to determine the effects of cannabinoids on nociceptive neurotransmission. Cannabinoids have been observed to markedly decrease signalling in specific neural pathways that transmit messages about pain. These effects were found to be due to the suppr...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(02)00252-8
更新日期：2002-08-01 00:00:00
abstract：:The aromatic amine 2-acetylaminofluorene (AAF) produced neoplasms in diverse target organs of many animal species. AAF was DNA-reactive after N-hydroxylation by CYP1A2 in the liver and nitrenium ion formation at the target site. In mouse bladder, AAF-DNA adducts were proportional to dose. An epigenetic component for t...
journal_title：Pharmacology & therapeutics
pub_type： 共识发展会议,杂志文章,评审
doi：10.1016/0163-7258(96)00063-0
更新日期：1996-01-01 00:00:00
abstract：:In the past 4 years, RNA interference (RNAi) has become widely used as an experimental tool to analyse the function of mammalian genes, both in vitro and in vivo. By harnessing an evolutionary conserved endogenous biological pathway, first identified in plants and lower organisms, double-stranded RNA (dsRNA) reagents ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.03.004
更新日期：2005-08-01 00:00:00
abstract：:Glutathione (GSH) fulfills several essential functions: Detoxification of free radicals and toxic oxygen radicals, thiol-disulfide exchange and storage and transfer of cysteine. GSH is present in all mammalian cells, but may be especially important for organs with intense exposure to exogenous toxins such as the liver...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(91)90029-l
更新日期：1991-12-01 00:00:00
abstract：:Canonical Wnt signaling is a highly conserved pathway with a prominent role in embryogenic development, adult tissue homeostasis, cell polarization, stem cell biology, cell differentiation, and proliferation. Furthermore, canonical Wnt signaling is of pivotal importance in the pathogenesis of a number of cancer types ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.11.001
更新日期：2016-01-01 00:00:00
abstract：:Chemoresistance, radioresistance, and the challenge of achieving complete resection are major driving forces in the search for more robust and targeted anticancer therapies. Targeting the DNA damage response has recently attracted research interest, as these processes are enhanced in tumour cells. The major replicatio...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107518
更新日期：2020-06-01 00:00:00
abstract：:Thoracic aortic aneurysms (TAAs) are a potential life-threatening disease with limited pharmacological treatment options. Current treatment options are aimed at lowering aortic hemodynamic stress, predominantly with β-adrenoceptor blockers. Increasing evidence supports a role for the renin-angiotensin system (RAS) in ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2011.04.002
更新日期：2011-07-01 00:00:00
abstract：:Myocarditis is a heterogeneous group of disorders defined by inflammation of the heart muscle. The primary clinical manifestations of myocarditis are heart failure and sudden death in children and young adults. Numerous interventions have been investigated for the treatment of myocarditis, including broad spectrum alt...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.03.006
更新日期：2016-05-01 00:00:00
abstract：:G protein-gated inwardly rectifying potassium channels (Kir3/GirK) are important for maintaining resting membrane potential, cell excitability and inhibitory neurotransmission. Coupled to numerous G protein-coupled receptors (GPCRs), they mediate the effects of many neurotransmitters, neuromodulators and hormones cont...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2021.107808
更新日期：2021-01-18 00:00:00
abstract：:Metabolic diseases have a tremendous impact on human morbidity and mortality. Numerous targets regulating adenosine monophosphate kinase (AMPK) have been identified for treating the metabolic syndrome (MetS), and many compounds are being used or developed to increase AMPK activity. In parallel, the cyclic nucleotide p...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107475
更新日期：2020-04-01 00:00:00
abstract：:The tumor microenvironment is increasingly recognized as a major factor influencing the success of therapeutic treatments and has become a key focus for cancer research. The progressive growth of a tumor results in an inability of normal tissue blood vessels to oxygenate and provide sufficient nutritional support to t...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2015.06.006
更新日期：2015-09-01 00:00:00
abstract：:Glucose-6-phospate dehydrogenase (G6PD) deficiency is estimated to affect more than 400 million people world-wide. This X-linked genetic deficiency puts stress on red blood cells (RBC), which may be further augmented under certain pathophysiological conditions and drug treatments. These conditions can cause hemolytic ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2020.107788
更新日期：2020-12-14 00:00:00
abstract：:Ion channels play key roles in determining smooth muscle tone by setting the membrane potential and allowing Ca2+ influx. Perhaps not surprisingly, therefore, they also provide targets for neurotransmitters and other messengers that act on smooth muscle. Application of patch-clamp and molecular biology techniques and ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(97)87271-3
更新日期：1997-01-01 00:00:00
abstract：:There are at least two types of cannabinoid receptors, CB1 and CB2, both coupled to G-proteins. CB1 receptors are present in the central nervous system and CB1 and CB2 receptors in certain peripheral tissues. The existence of endogenous cannabinoid receptor agonists has also been demonstrated. These discoveries have l...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(97)82001-3
更新日期：1997-01-01 00:00:00
abstract：:The 90-kDa molecular chaperone family (which comprises, among other proteins, the 90-kDa heat-shock protein, hsp90 and the 94-kDa glucose-regulated protein, grp94, major molecular chaperones of the cytosol and of the endoplasmic reticulum, respectively) has become an increasingly active subject of research in the past...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(98)00013-8
更新日期：1998-08-01 00:00:00
abstract：:Primaquine is the only antimalarial drug available to clinicians for the treatment of relapsing forms of malaria. Primaquine development and usage dates back to the 1940s and has been administered to millions of individuals to treat and eliminate malaria infections. Primaquine therapy is not without disadvantages, how...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2016.03.011
更新日期：2016-05-01 00:00:00
abstract：:The gene MUC1 encodes a large membrane-associated glycoprotein, previously termed polymorphic epithelial mucin and now known as MUC1. The majority of the extracellular domain is made up of tandem repeats of 20 amino acids. In some epithelial malignancies, MUC1 is up-regulated, and as a result of changes in glycosyl an...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/s0163-7258(99)00003-0
更新日期：1999-04-01 00:00:00
abstract：:In spite of a lack of compounds acting selectively at the 5-hydroxytryptamine (5-HT)1B and 5-HT1D receptor subtypes, by cross-relating the available data, this review attempts to tentatively assign behavioural and other in vivo correlates of these receptor subtypes. In addition, a summary of data from microdialysis st...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/0163-7258(94)90051-5
更新日期：1994-01-01 00:00:00
abstract：:For many years, warfarin was the only effective oral anticoagulant to prevent and treat thromboembolism. Nevertheless, its clinical use is limited by a narrow therapeutic window, extensive drug interactions, need of strict dietary control and frequent monitoring. The pharmacological response is also unpredictable and ...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2010.09.005
更新日期：2011-02-01 00:00:00
abstract：:Major depression is a debilitating and recurrent disorder with a substantial lifetime risk and a high social cost. Depressed patients generally display co-morbid symptoms, and depression frequently accompanies other serious disorders. Currently available drugs display limited efficacy and a pronounced delay to onset o...
journal_title：Pharmacology & therapeutics
pub_type： 杂志文章,评审
doi：10.1016/j.pharmthera.2005.11.006
更新日期：2006-05-01 00:00:00
