Abstract:
:Current strategies in pharmaceutical research comprise two methodologically different but complementary approaches for lead finding purposes, namely the random screening of compound libraries and the structure-based effort, commonly termed rational drug design. The structure-based approach is aimed to exploit 3D structure data of the molecular components involved in the molecular recognition event that underlies the attempt to therapeutically modulate the biological function of a macromolecular target with proven pathophysiological relevance for a disease state. In this context, G protein-coupled receptors (GPCRs) constitute the most prominent family of validated drug targets within biomedical research, since approximately 60 % of approved drugs elicit their therapeutic effects by selectively addressing members of that target family. From a 3D structure point of view, these transmembrane signal transduction systems represent the most challenging task for structure determination, which is due to the heterogeneous and fine-balanced environment conditions that are necessary for structural and functional integrity of the receptor protein. This contribution will address the different concepts to derive structurally relevant information on the transmemebrane seven-helix protein (7TM) domain of GPCRs with special emphasis laid on the multidisciplinarity of the applied methodologies. The current status of electron-cryo-microscopy on 2D crystals and even high-resolution x-ray crystallography on 7TM proteins will be introduced highlighting the transferability of the emerging structural principles onto the GPCR superfamily. Special techniques from bioinformatics and homology-related molecular modeling in combination with tailor-made protein simulation methodologies complement the experimentally derived data, in that they facilitate the 3D structure generation and structure validation process. This contribution summarises the most recent results of GPCR structure studies with the aim to underline the impact of structure data not only for the purpose of rationalising structure-activity data on low-molecular weight antagonists within the context of a protein binding pocket, but also for a better understanding of e.g. mutagenesis experiments, thus qualifying GPCR structure models as valid communication platforms establishing a functional link between molecular biology, biophysics, bioinformatics and organic chemistry in a highly efficient manner.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Müller Gdoi
10.2174/0929867003374534subject
Has Abstractpub_date
2000-09-01 00:00:00pages
861-88issue
9eissn
0929-8673issn
1875-533Xjournal_volume
7pub_type
杂志文章,评审abstract::DNA mutation is a very important step in carcinogenesis and elevated levels of oxidative DNA damage have been monitored in a variety of tumors. The discovery of the role of free radicals in cancer has led to a new medical approach. Minimizing oxidative damage may be a significant advance in the prevention or treatment...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/09298673113203690142
更新日期:2013-01-01 00:00:00
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journal_title:Current medicinal chemistry
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更新日期:2005-01-01 00:00:00
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journal_title:Current medicinal chemistry
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journal_title:Current medicinal chemistry
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doi:10.2174/0929867324666171113120810
更新日期:2019-01-01 00:00:00
abstract::β-Aryl-β-amino acids constitute very useful scaffolds able to lead, via various intra-molecular cyclisation reactions, to a great diversity of cyclic derivatives with numerous biological and therapeutic properties. The present article aims at reporting an exhaustive overview of these ring-closure sequences and their a...
journal_title:Current medicinal chemistry
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更新日期:2010-01-01 00:00:00
abstract::This review summarizes our knowledge of biochemical, biological and medical applications and properties of phosphinic acid compounds. Phosphinic acid compounds (phosphinates) are derivatives of phosphinic acid H2P(O)(OH). The major attention of this article is focused on applications of phosphinates of a pseudopeptide...
journal_title:Current medicinal chemistry
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doi:10.2174/0929867003374831
更新日期:2000-06-01 00:00:00
abstract::Protein-based polymers are some of the most promising candidates for a new generation of innovative biomaterials as recent advances in genetic-engineering and biotechnological techniques mean that protein-based biomaterials can be designed and constructed with a higher degree of complexity and accuracy. Moreover, thei...
journal_title:Current medicinal chemistry
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abstract::Drug resistance is one of the major obstacles limiting the success of cancer chemotherapy. Biological mechanisms contributing to drug resistance may be present de novo and related to inherent features or may be raised after exposure to anticancer drugs. In recent years, both clinical observations and experimental stud...
journal_title:Current medicinal chemistry
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更新日期:2011-01-01 00:00:00
abstract::Semicarbazide-sensitive amine-oxidase (SSAO) is present in various human tissues and in plasma. Oxidative deamination of short-chain aliphatic amines is catalyzed by this enzyme to afford the corresponding aldehydes, ammonia and hydrogen peroxide. Methylamine and aminoacetone have been recognized to be physiological s...
journal_title:Current medicinal chemistry
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更新日期:2004-05-01 00:00:00
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journal_title:Current medicinal chemistry
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更新日期:2017-01-01 00:00:00
abstract::Tuberculosis (TB) is the leading cause of mortality due to a single infectious agent. The currently used combination drug regimens produce cure rates that exceed 95%, given good patient adherence during the multiple months treatment period. However the recent surge in HIV infections and the synergy between HIV and TB ...
journal_title:Current medicinal chemistry
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更新日期:2008-01-01 00:00:00
abstract::Borderline Personality Disorder (BPD) is a common disorder in psychiatric practice and drugs are widely used in its treatment, targeting symptom clusters, such as affective dysregulation, impulsive-behavioural dyscontrol, and cognitive-perceptual symptoms. In last period, a growing number of studies on pharmacological...
journal_title:Current medicinal chemistry
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更新日期:2011-01-01 00:00:00
abstract::Potent enzyme inhibitors have long been recognized as powerful tools for assessing the physiological roles of enzymes and have led to the therapeutic drugs able to modulate their activities in vivo. However, to be valuable tools such inhibitors should be selective so that they do not interfere with other members of th...
journal_title:Current medicinal chemistry
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更新日期:2002-02-01 00:00:00
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journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2015-01-01 00:00:00
abstract::The neuropeptide substance P (SP) shows a widespread distribution in both the central and peripheral nervous systems and it is known that after binding to the neurokinin-1 (NK-1) receptors, SP regulates many biological functions in the central nervous system such as emotional behaviour, stress, depression, anxiety, em...
journal_title:Current medicinal chemistry
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更新日期:2011-01-01 00:00:00
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journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867013373192
更新日期:2001-05-01 00:00:00
abstract::Hypoxia in tumor cells is characterized by a lack of oxygen resulting from reduced blood supply to the surrounding tissue, and is a common characteristic of solid tumors as a consequence of rapid cell growth. Hypoxia in tumors is a predictor of both resistance to chemotherapy and of a metastatic/aggressive form of can...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/0929867322666151021111016
更新日期:2015-01-01 00:00:00
abstract::Glycosaminoglycans, highly charged polycarboxylated, polysulfated polysaccharides, are an important class of therapeutic agents and investigational drug candidates. Heparin has been widely used as a clinical anticoagulant for over 60 years. Low molecular weight heparins have begun to displace heparin and recently a sy...
journal_title:Current medicinal chemistry
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doi:10.2174/0929867033456891
更新日期:2003-10-01 00:00:00
abstract::Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder affecting women in reproductive age. Although the etiology of PCOS remains unclear, it is believed to result from genetic, environmental and behavioral interactions. Women with PCOS have higher lifetime risk for cardiovascular disease...
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pub_type: 杂志文章,评审
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更新日期:2014-01-01 00:00:00
abstract::In modern industrialized societies, people are exposed to thousands of naturally occurring and synthetic chemicals throughout their lifetime. Although certain occupational chemicals are known to be carcinogenic in humans, it has been difficult to definitively determine the adverse health effects of many environmental ...
journal_title:Current medicinal chemistry
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更新日期:2008-01-01 00:00:00
abstract::Tumor necrosis factor (TNF) is a cytokine with well known anticancer properties and is being utilized as anticancer agent for the treatment of patients with locally advanced solid tumors. However, TNF role in cancer biology is debated. In fact, in spite of the wealth of evidence supporting its antitumor activity, the ...
journal_title:Current medicinal chemistry
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更新日期:2010-01-01 00:00:00
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更新日期:2019-01-01 00:00:00
abstract::Phosphonated nucleosides represent a promising alternative in the improvement of the biological activity of nucleoside analogues in antiviral and anticancer chemotherapy. The basic concept, the chemistry, the different structural modifications and their effects on the antiviral potency will be discussed in this review...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2006-01-01 00:00:00
abstract::With the increasing production of engineered nanomaterials (ENMs) exploited in many consumer products, a wider number of people is expected to be exposed to such materials in the near future, both in occupational and environmental settings. This has raised concerns about the possible implications on public health. In ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2012-01-01 00:00:00
abstract::The present article reviews interesting cationic liposomes (cationic transfection lipids) with novel cationic cholesterol derivatives, a new strategy in gene transfection developed by our group and the presently accepted molecular mechanism of gene transfection. Use of confocal laser scanning microscopy and atomic for...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2003-07-01 00:00:00
abstract::Trypanosomatids are a group of flagellated unicellular eukaryotes, causing serious human diseases including Chagas disease (Trypanosoma cruzi), sleeping sickness (Trypanosoma brucei spp.) and Leishmaniasis (Leishmania spp.). The second messenger cAMP is involved in numerous and fundamental processes in these parasites...
journal_title:Current medicinal chemistry
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更新日期:2019-01-01 00:00:00
abstract::The existence of functional NT/dopamine interactions in the central nervous system has been extensively documented. Among others, a possible molecular mechanism underlying the NT-induced modulation of dopamine release is a direct antagonistic NTS(1)/D(2) receptor interaction. More recently, neurochemical experiments a...
journal_title:Current medicinal chemistry
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更新日期:2012-01-01 00:00:00
abstract::Although resin-based chemistry offers many practical advantages over conventional solution phase for the synthesis of combinatorial libraries, effective monitoring of reactions conducted on the support remains a challenge. A number of techniques have been developed to enable the analysis of solid phase organic synthes...
journal_title:Current medicinal chemistry
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更新日期:2002-12-01 00:00:00
abstract:BACKGROUND:Pregnancy specific β1-glycoproteins (PSGs) have long been recognized as trophoblast quality and embryo viability markers. However, biological roles of PSGs remain obscure, and structure/function relationships to other feto-placental proteins as well as implications for drug design have not been reviewed. Thi...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
abstract::Novel molecular genetic approaches, at genome-scale in different species allowed characterizing genes that have undergone recent selection. The interest in this research field is not limited to the natural curiosity about our evolutionary past, but it is also to identify novel susceptibility genes for neuropsychiatic ...
journal_title:Current medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2010-01-01 00:00:00