Abstract:
:Although the proteins in all the current major classes considered to be druggable are folded in their native states, intrinsically disordered proteins (IDPs) are becoming attractive candidates for therapeutic intervention by small drug-like molecules. IDPs are challenging targets because they exist as ensembles of structures, thereby making them unsuitable for standard rational drug design approaches, which require the knowledge of the three-dimensional structure of the proteins to be drugged. As we review in this chapter, several different small molecule strategies are currently under investigation to target IDPs, including: (i) to stabilise IDPs in their natively disordered states, (ii) to inhibit interactions with ordered or disordered protein partners, and (iii) to induce allosteric inhibition. In this context, biophysical techniques, including in particular nuclear magnetic resonance (NMR) spectroscopy and small-angle X-ray scattering (SAXS) coupled with molecular dynamics simulations and chemoinformatics approaches, are increasingly used to characterize the structural ensembles of IDPs and the specific interactions that they make with their binding partners. By analysing the results of recent studies, we describe the main structural features that may render IDPs druggable, and describe techniques that can be used for drug discovery programs focused on IDPs.
journal_name
Adv Exp Med Bioljournal_title
Advances in experimental medicine and biologyauthors
Joshi P,Vendruscolo Mdoi
10.1007/978-3-319-20164-1_13subject
Has Abstractpub_date
2015-01-01 00:00:00pages
383-400eissn
0065-2598issn
2214-8019journal_volume
870pub_type
杂志文章,评审abstract::The world is facing an ever-increasing problem with antibiotic resistant bacteria and we are rapidly heading for a post-antibiotic era. There is an urgent need to investigate alterative treatment options while there are still a few antibiotics left. Bacteriophages are viruses that specifically target bacteria. Before ...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-81-322-1777-0_7
更新日期:2014-01-01 00:00:00
abstract::The transient length response of the cat papillary muscle in Ba2+-contracture to step tension reduction was found to comprise four different phases. It is tentatively suggested that the transient response is mostly determined by the kinetics of the attachment and detachment of cross-bridges between actin and myosin fi...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4684-4703-3_82
更新日期:1984-01-01 00:00:00
abstract::The ruffled border is the most specific marker of the active osteoclast (OC) as it forms only when the cell is resorbing bone. We provide evidence that this complex cytoskeletal structure reflects insertion of the lysosomal vesicles into the bone-apposed plasma membrane under the aegis of the Ca-sensing, exocytic prot...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4419-1050-9_11
更新日期:2010-01-01 00:00:00
abstract::The quantification of tissue oxygen by frequency or time domain methods has been discussed in a number of prior publications where the meaning of the tissue hemoglobin oxygen saturation was unclear and where the CW instruments were unsuitable for proper quantitative measurements [1, 2]. The development of the IQ Phase...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4615-0075-9_2
更新日期:2003-01-01 00:00:00
abstract::Xeno-transplantation of pancreatic islets represents a promising therapeutic alternative for the treatment of type 1 diabetes mellitus. However, potent innate immune responses induced shortly after the transplantation of donor islets to the recipient, comprising the Instant Blood Mediated Immune Reaction (IBMIR), exer...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-18603-0_11
更新日期:2015-01-01 00:00:00
abstract::The basic physical and functional unit of heredity; made up of DNA, they act as instructions to make proteins. There are about 20,000-25,000 genes in humans, with size varying from a few hundred DNA bases to more than 2 million bases. Most genes are the same in all people; less than 1% differ. Each person has two copi...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-95046-4_7
更新日期:2018-01-01 00:00:00
abstract::The inner blood-retinal barrier (inner BRB) is created by complex tight junctions of retinal capillary endothelial cells. Although this barrier prevents the free diffusion of substances between the circulating blood and the neural retina, the inner BRB efficiently supplies nutrients to the retina and removes endobioti...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:
更新日期:2012-01-01 00:00:00
abstract::We review here the covalent photo-binding induced by visible light between the essential amino acid tryptophan and the vitamin riboflavin. We discuss the biological implications of this photoadduct in relation to the hepatotoxic and cytotoxic effect associated to parenteral nutrients and to culture media exposed to th...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4899-2626-5_3
更新日期:1991-01-01 00:00:00
abstract::Identification of thyroid stem cells in the past few years has made important contributions to our understanding of the cellular and molecular mechanisms that induce tissue regeneration and repair. Embryonic stem (ES) cells and induced-pluripotent stem cells have been used to establish reliable protocols to obtain mat...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-3-030-24108-7_5
更新日期:2019-01-01 00:00:00
abstract::Feedback from muscle afferents is essential for locomotion to be functional under changing external conditions. In this article, we review the role of afferent feedback in adapting locomotor activity to transient and more sustained changes in sensory input in reduced and walking cat preparations. Much of the work on m...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4615-0713-0_40
更新日期:2002-01-01 00:00:00
abstract::Mortality from plague is high if not treated with the proper antibiotics within 18-24 hours after onset of symptoms. The process of antibiotic susceptibility determination of Yersinia pestis isolated from blood samples may extend from 4 to more than 7 days, since the in vitro growth is very slow. To accelerate this pr...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-0-387-72124-8_31
更新日期:2007-01-01 00:00:00
abstract::Proteomics involves large-scale comprehensive study of specific proteomes which have been widely used in the field of biomarker discovery, drug development, disease diagnosis and therapy. Comprehensive proteomics involve two or more proteomics approaches that are confirmatory, complementary, and/or synergistic. Obstru...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-3-030-15950-4_32
更新日期:2019-01-01 00:00:00
abstract::Intermittent measurement of blood pressure (BP) is frequently performed in newborn babies under intensive care using an inflatable cuff encircling either the arm or leg. This paper describes work aimed at achieving continuous beat-by-beat measurement of the arterial pressure waveform by means of a finger cuff, the pre...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4613-1927-6_56
更新日期:1987-01-01 00:00:00
abstract::Chemometrics has been a fundamental discipline for the development of metabolomics, while symbiotically growing with it. From design of experiments, through data processing, to data analysis, chemometrics tools are used to design, process, visualize, explore and analyse metabolomics data.In this chapter, the most comm...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-3-319-47656-8_7
更新日期:2017-01-01 00:00:00
abstract::Better understanding of central nervous system (CNS) molecules can include the identification of new molecules and their receptor systems. Discovery of novel proteins and elucidation of receptor targets can be accomplished using mass spectrometry (MS). We describe a case study of such a molecule, which our lab has stu...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-3-319-06068-2_25
更新日期:2014-01-01 00:00:00
abstract::The respiratory control system is not fully developed in newborn, and data suggest that adequate nutrition is important for the development of the respiratory control system. Infants need to be fed every 2-4 h to maintain appropriate energy levels, but a skip of feeding can occur due to social economical reasons or mi...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-3-319-18440-1_20
更新日期:2015-01-01 00:00:00
abstract::Retinoids clearly show both prophylactic and therapeutic effects against many kinds of neoplasm. Vitamin A deficiency and vitamin A excess, which are very different states clinically and metabolically, should be separately considered relative to carcinogenesis. The anticancer effects of retinoids and related compounds...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4613-1835-4_28
更新日期:1986-01-01 00:00:00
abstract::There is evidence that the same mycobacterial heat shock proteins (Mtb-HSPs), especially HSP16, the main marker of mycobacteria dormant stage, occur in sarcoid tissues and in circulated immune complexes and prompt the immune responses against the different genetic background, leading to the development of acute sarcoi...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/5584_2015_139
更新日期:2015-01-01 00:00:00
abstract::The cerebellum, and the olivo-cerebellar system in particular, may be the central mechanism of a neural clock that provides a rhythmic neural signal used to time motor and cognitive processes. Several independent lines of evidence support this hypothesis. First, the resting membrane potential of neurons in the inferio...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4939-1782-2_9
更新日期:2014-01-01 00:00:00
abstract::Near infrared spectroscopy (NIRS) may provide valuable insight into the determinants of exercise performance. We examined the effects of severe hypoxia on cerebral (prefrontal lobe) and muscle (gastrocnemius) oxygenation at rest and during a fatiguing task. After a 15-min rest, 15 healthy subjects (age 25.3 +/- 0.9 yr...
journal_title:Advances in experimental medicine and biology
pub_type: 临床试验,杂志文章
doi:10.1007/978-0-387-85998-9_49
更新日期:2009-01-01 00:00:00
abstract::Protein-protein associations represent the building blocks of biological systems. The classification of different types of protein association is fundamental to an understanding of the interactions they exhibit. A protein association can be classified as homo- (identical components) or hetero- (non-identical component...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4614-3229-6_3
更新日期:2012-01-01 00:00:00
abstract::The goals of constructing epilepsy models are (1) to develop approaches to prophylaxis of epileptogenesis following cortical injury; (2) to devise selective treatments for established epilepsies based on underlying pathophysiological mechanisms; and (3) use of a disease (epilepsy) model to explore brain molecular, cel...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-94-017-8914-1_18
更新日期:2014-01-01 00:00:00
abstract::Infantile colic, constipation, functional abdominal pain (FAP), and irritable bowel syndrome (IBS) are the most common functional gastrointestinal disorders (FGID). This chapter will review current evidence on the role of probiotics in the treatment of these FGID. The etiology of FGID is considered multifactorial, but...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/5584_2018_321
更新日期:2019-01-01 00:00:00
abstract::Personalized medicine has been driven by improvements in genomic sequencing and analysis. For several diseases, in particular cancers, it has for nearly a decade been standard clinical practice to analyze the genome and expression of the genes of patients. The results are reflected directly in the treatment plan for t...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-981-15-4494-1_15
更新日期:2020-01-01 00:00:00
abstract::An integrated left ventricular (LV) model is used to solve, simultaneously and interactively, the LV mechanics, the coronary blood flow and capillary and interstitial fluid and mass transport, and to analyze the LV behavior under normal as well as pathological conditions. Accounting for the interstitial fluid mass bal...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4615-2946-0_21
更新日期:1993-01-01 00:00:00
abstract::Initial attempts to model urinary folate reabsorption using cultures of HPT cells on porous filter inserts produced disappointing results in that large amounts of 5M were transported across the epithelial monolayer in a nonspecific manner. Since the impermeable molecule inulin was also transported, there apparently ex...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-1-4615-2960-6_155
更新日期:1993-01-01 00:00:00
abstract::Lead (Pb2+) is a developmental neurotoxicant that causes lifelong cognitive dysfunctions. In particular, Pb2+-induced frontoexecutive dysfunctions emerge later in life when the cortex is fully myelinated, thereby permitting the ability to assess the extent to which Pb2+ has developmentally impacted higher order cognit...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章
doi:10.1007/978-981-13-8023-5_70
更新日期:2019-01-01 00:00:00
abstract::Stem cells provide for all of the tissues in our body during embryogenesis. In adult organisms, they can be found as rare populations of tissue-specific stem cells in quiescent states, although they can still regenerate damaged tissues. Astonishingly, these cells are retained in tissues even post-mortem. There have be...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/5584_2020_492
更新日期:2020-01-01 00:00:00
abstract::The ubiquitin proteasome pathway is one of the major regulatory tools used by eukaryotic cells. The evolutionarily conserved cullin family proteins can assemble as many as >600 distinct E3 ubiquitin ligase complexes that regulate diverse cellular pathways. In most of Cullin-RING ubiquitin ligase (CRL) complexes, separ...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-981-15-1025-0_13
更新日期:2020-01-01 00:00:00
abstract::The silicone tube model of regeneration has proved to be an invaluable tool for experimental studies aimed at understanding expression of growth factors during normal and abnormal metabolic states of regeneration. Since the morphological parameters of nerve growth and myelination are well-defined and easily identified...
journal_title:Advances in experimental medicine and biology
pub_type: 杂志文章,评审
doi:10.1007/978-1-4615-3448-8_5
更新日期:1992-01-01 00:00:00