Abstract:
:In this review we discuss the role of protonation states in receptor-ligand interactions, providing experimental evidences and computational predictions that complex formation may involve titratable groups with unusual pKa's and that protonation states frequently change from unbound to bound states. These protonation changes result in proton uptake/release, which in turn causes the pH-dependence of the binding. Indeed, experimental data strongly suggest that almost any binding is pH-dependent and to be correctly modeled, the protonation states must be properly assigned prior to and after the binding. One may accurately predict the protonation states when provided with the structures of the unbound proteins and their complex; however, the modeling becomes much more complicated if the bound state has to be predicted in a docking protocol or if the structures of either bound or unbound receptor-ligand are not available. The major challenges that arise in these situations are the coupling between binding and protonation states, and the conformational changes induced by the binding and ionization states of titratable groups. In addition, any assessment of the protonation state, either before or after binding, must refer to the pH of binding, which is frequently unknown. Thus, even if the pKa's of ionizable groups can be correctly assigned for both unbound and bound state, without knowing the experimental pH one cannot assign the corresponding protonation states, and consequently one cannot calculate the resulting proton uptake/release. It is pointed out, that while experimental pH may not be the physiological pH and binding may involve proton uptake/release, there is a tendency that the native receptor-ligand complexes have evolved toward specific either subcellular or tissue characteristic pH at which the proton uptake/release is either minimal or absent.
journal_name
Curr Pharm Desjournal_title
Current pharmaceutical designauthors
Petukh M,Stefl S,Alexov Edoi
10.2174/1381612811319230004subject
Has Abstractpub_date
2013-01-01 00:00:00pages
4182-90issue
23eissn
1381-6128issn
1873-4286pii
CPD-EPUB-20121120-1journal_volume
19pub_type
杂志文章,评审abstract::We have gained considerable insight and understanding about the etiology, embryogenesis of the myocardium, genetic background, diagnosis and outcome of left ventricular non-compaction (LVNC) over the last 2 decades. LVNC has a distinct morphological appearance with a thickened, two-layered myocardium consisting of an ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161282104141204143212
更新日期:2015-01-01 00:00:00
abstract::The triggering receptor expressed on myeloid cells (TREM)-1 is a member of the Ig-like immunoregulatory receptor family and a major amplifier of innate immune responses. TREM- 1 has been implicated in the development and perpetuation of a number of inflammatory disorders, and soluble TREM-1 levels are a clinically val...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666160826110539
更新日期:2016-01-01 00:00:00
abstract::Bisphosphonates are widely use for pathologies such as osteoporosis, Paget's disease or bone metastasis. However, their potent antiresorptive properties open new therapeutic opportunities for other conditions associated with an increased focal or systemic bone remodelling. Moreover, apart from their antiresorptive act...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210793563626
更新日期:2010-01-01 00:00:00
abstract::Mitochondria fulfill a number of essential cellular functions, being recognized that the strict regulation of the structure, function and turnover of these organelles is an immutable control node for the maintenance of neuronal integrity and homeostasis. Many lines of evidence posit that mitochondria constitute a conv...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211798072490
更新日期:2011-01-01 00:00:00
abstract::The pivotal therapeutic role of myocardial metabolic modulation in ischemic heart disease (IHD) is increasingly recognized. Among the others, inhibitors of free fatty acids (FFA) oxidation have been consistently shown to play an important role in the therapeutic strategy of IHD patients. Additionally, abnormalities of...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209787582093
更新日期:2009-01-01 00:00:00
abstract::The state-of-the-art in the investigation of drugs release from Silica-based ordered Mesoporous Materials (SMMs) is reviewed. First, the SMM systems used like host matrixes are described. Then, the model drugs studied until now, including their pharmacological action, structure and the mesoporous matrix employed for e...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612822666151106121419
更新日期:2015-01-01 00:00:00
abstract::Benzodiazepines (BZs) have been widely investigated in terms of clinical efficacy, factors underlying dependence, associated cognitive impairments, and interactions with psychotherapy for anxiety control. However, few studies have systematically considered manner of BZ administration in relation to these variables. St...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612023396744
更新日期:2002-01-01 00:00:00
abstract::Drug design based on the structure of specific enzymes playing a role in carcinogenesis, e.g. tyrosine kinases, has been successful at identifying novel effective anticancer drugs. In contrast, no success has been achieved in drug design attempts, in which transcription factors or DNA-transcription factor complexes in...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161207781757097
更新日期:2007-01-01 00:00:00
abstract::Monocytes are leading component of the mononuclear phagocytic system that play a key role in phagocytosis and removal of several kinds of microbes from the body. Monocytes are bone marrow precursor cells that stay in the blood for a few days and migrate towards tissues where they differentiate into macrophages. Monocy...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190102104642
更新日期:2018-01-01 00:00:00
abstract::Carboxylic acids are an important natural component as a final product or intermediates for syntheses. They are produced in plants, animals and also as products from biotechnological processes. This review presents the use of single hydroxide particles and layered double hydroxides as alternative adsorbents to remove ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666191226103623
更新日期:2020-01-01 00:00:00
abstract::Serotonin (5-HT) is one of the main transmitters in the nervous system. Serotonergic neurons in the raphe nuclei in the brainstem innervate most parts of the central nervous system including motoneurons in the spinal cord and brainstem. This review will focus on the modulatory role that 5-HT exerts on motoneurons and ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990341
更新日期:2013-01-01 00:00:00
abstract::A recent meta-analysis showed that the mean age of onset of psychosis among cannabis users was almost three years earlier than that of non-cannabis users. However, because cannabis users usually smoke tobacco, the use of tobacco might independently contribute to the earlier onset of psychosis. We aimed to use meta-ana...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,meta分析
doi:10.2174/138161212802884816
更新日期:2012-01-01 00:00:00
abstract::P2Y12 adenosine di-phosphate (ADP) receptor antagonists are critical to reduce thrombotic recurrences in acute coronary syndromes patients and for those undergoing percutaneous coronary revascularization. Multiple lines of evidence suggest that the level of on-treatment platelet reactivity inhibition with P2Y12 ADP re...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212803251934
更新日期:2012-01-01 00:00:00
abstract::Post-traumatic stress disorder (PTSD) is an anxiety disorder that develops after experiencing trauma. Actual therapies do not help majority of patients with PTSD. Moreover, extinguished fear memories usually reappear in the individuals when exposed to trauma cues. New drugs to reduce the impact of conditioned cues in ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612821666150710145250
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Central serous chorioretinopathy (CSC) is the fourth most frequent retinal disorder in terms of prevalence. It typically occurs in young subjects and affects men more often than women. CSC is characterized by serous retinal detachment (SRD) involving mainly the macular area. The clinical course is usually se...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612825666190123165914
更新日期:2018-01-01 00:00:00
abstract::Iron oxide (Fe₃O₄) nanoparticles (IONPs) have received much attention for their utility in biomedical applications such as magnetic resonance imaging, drug delivery and hyperthermia. Recent studies reported that IONPs induced cytotoxicity in mammalian cells. However, little is known about the genotoxicity of IONPs fol...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612811319370011
更新日期:2013-01-01 00:00:00
abstract::The common mechanism of action of aspirin and the chemically unrelated non-steroidal anti-inflammatory drugs (NSAIDs) is the inhibition of prostaglandin (PG) production due to interference with the enzymatic activity of cyclooxygenase (COX). These agents have long been used as effective treatments for arthritis. The r...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612003398753
更新日期:2000-11-01 00:00:00
abstract::LIM (Lin-11, Isl-1, Mec-3), RING (Really interesting new gene), PHD (Plant homology domain) and MYND (myeloid, Nervy, DEAF-1) domains are all zinc-binding domains that ligate two zinc ions. Unlike the better known classical zinc fingers, these domains do not bind DNA, but instead mediate interactions with other protei...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161209789271861
更新日期:2009-01-01 00:00:00
abstract::The diatomic molecule of oxygen contains two uncoupled electrons and can therefore undergo reduction, yielding several different oxygen metabolites, which are collectively called Reactive Oxygen Species or ROS. They are invariably produced in aerobic environments through a variety of mechanisms, which include electron...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612043384664
更新日期:2004-01-01 00:00:00
abstract::In recent years, there has been an exciting focus of research attempting to understand neuropsychiatric disorders from a holistic perspective in order to determine the role of gut microbiota in the aetiology and pathogenesis of such disorders. Thus, the possible therapeutic benefits of targeting gut microbiota are bei...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612826666200122153541
更新日期:2020-01-01 00:00:00
abstract::Over the last three decades, neoplasms have become the largest cause of human mortality due to both high tumor incidence and mortality. Chemotherapy is one of the main therapies employed to treat neoplasms. Although classical genotoxic drugs, such as cyclophosphamide, 5-FU, cisplatin and doxorubicin have been applied ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/1381612823666170720113216
更新日期:2017-11-16 00:00:00
abstract::In the stomach, pre-absorptive perception of food constituents is of particular importance in maintaining secretion and motility that matches the quantity and quality of nutrients. Products of food protein hydrolysis, free amino acids and short peptides, are the most potent chemical stimulants of the gastric phase of ...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/13816128113199990581
更新日期:2014-01-01 00:00:00
abstract:Background:Capsinoids (CSN), the novel non-pungent capsaicin analogs have been reported to promote metabolic health and exercise tolerance. However, the effect of CSN on fat oxidation and changes in skeletal muscle glycogen levels during post-exercise recovery has not been investigated in humans. Purpose:We examined t...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/1381612826666200824104856
更新日期:2020-08-23 00:00:00
abstract::Understanding of the roles of RNAs within the cell has changed and expanded dramatically during the past few years. Based on fundamentally new insights it is now increasingly possible to employ RNAs as highly valuable tools in molecular biology and medicine. At present, the most important therapeutic strategies are ba...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210791792813
更新日期:2010-01-01 00:00:00
abstract::Transpeptidation reactions result in the formation of new peptide bonds and this can occur between two separate peptides or within the one peptide. These reactions are catalyzed by enzymes and when the N- and C-terminus of the one peptide are joined it results in the formation of cyclic proteins. Cyclization via head-...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161211798999410
更新日期:2011-12-01 00:00:00
abstract::Alzheimer's disease (AD) is the most common neurodegenerative disorder that affects the elderly. The increase of life-expectancy is transforming AD into a major health-care problem. AD is characterized by a progressive impairment of memory and other cognitive skills leading to dementia. The major pathogenic factor ass...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161210793176572
更新日期:2010-01-01 00:00:00
abstract::Tumour resistance to anticancer agents remains a challenge in oncological practice, because it results in exposure to toxicities, unnecessary costs and, most importantly, delay of a potentially more effective treatment. Drug uptake by tumours may be impaired by several resistance pathways. Reasons for primary resistan...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208786404344
更新日期:2008-01-01 00:00:00
abstract::Two morphological features may be seen as a main result of the cardiovascular cell damage caused by cigarette smoking: myocardial cell necrosis and smoke cardiomyopathy that, however, can lead to cell necrosis in case of chronic prolonged exposure to tobacco smoke. Both these pathological patterns recognise hypoxia as...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161208784746699
更新日期:2008-01-01 00:00:00
abstract::Guidelines for the treatment of hypertension allow a wide range of choices to the physicians; however some differences are present about the preferred drugs to start treatment. The most important aim remains an adequate decrease of blood pressure, something not perfectly obtained in the general population, but some cl...
journal_title:Current pharmaceutical design
pub_type: 杂志文章,评审
doi:10.2174/138161212799436575
更新日期:2012-01-01 00:00:00
abstract::Aim of the presented study was to investigate the role of stromal derived factor 1 (SDF-1α) in mobilizing stem cells in combination with endothelial progenitor cell (EPC) transplantation in a regenerative strategy for myocardial infarction therapy in a murine ischemia/reperfusion model. Initially bone marrow was eradi...
journal_title:Current pharmaceutical design
pub_type: 杂志文章
doi:10.2174/13816128113199990443
更新日期:2014-01-01 00:00:00