Abstract：
:STATs promote fundamental cellular processes, marking them as convergence points of many oncogenic and inflammatory pathways. Therefore, aberrant activation of STAT signaling is implicated in a plethora of human diseases, like cancer, inflammation and auto-immunity. Identification of STAT-specific inhibitors is the topic of great practical importance, and various inhibitory strategies are being pursued. An interesting approach includes peptides and peptide-like biopolymers, because they allow the manipulation of STAT signaling without the transfer of genetic material. Phosphopeptides and peptidomimetics directly target STATs by inhibiting dimerization. Despite that a large number of efficient peptide- based STAT3-specific inhibitors have been reported to date, none of them was able to meet the pharmacological requirements to serve as a potent anti-cancer drug. The existing limitations, like metabolic instability and poor cell permeability during in vivo tests, excluded these macromolecules from further clinical development. To overcome these liabilities, in the last five years many advances have been made to develop next generation STAT-specific inhibitors. Here we discuss the pitfalls of current STAT inhibitory strategies and review the progress on the development of peptide-like prodrugs directly targeting STATs. Novel strategies involve screening of high-complexity libraries of random peptides, as specific STAT3 or STAT5 DNA-binding inhibitors, to construct cell permeable peptide aptamers and aptides for cancer therapy. Another new direction is synthesis of negative dominant α-helical mimetics of the STAT3 N-domain, preventing oligomerization on DNA. Moreover, construction of phosphopeptide conjugates with molecules mediating cellular uptake offers new therapeutic possibilities in treatment of cancer, asthma and allergy.
journal_name
Curr Protein Pept Scijournal_title
Current protein & peptide scienceauthors
Szelag M,Wesoly J,Bluyssen HAdoi
10.2174/1389203716666151102103706subject
Has Abstractpub_date
2016-01-01 00:00:00pages
135-46issue
2eissn
1389-2037issn
1875-5550pii
CPPS-EPUB-71505journal_volume
17pub_type
杂志文章,评审abstract：:Members of the Really Interesting New Gene (RING) family of proteins are found throughout the cells of eukaryotes and function in processes as diverse as development, oncogenesis, viral replication and apoptosis. There are over 200 members of the RING family where membership is based on the presence of a consensus seq...
journal_title：Current protein & peptide science
pub_type： 杂志文章
doi：10.2174/1389203003381478
更新日期：2000-07-01 00:00:00
abstract：:Knowledge of the existence and structure of intermediates on the reaction pathway is necessary before specific details of the mechanism may be successfully resolved. However, enzymatic catalysis is an extremely fast process. This rapidity of enzyme-catalyzed reactions and the short life times of intermediates represen...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/138920309789351958
更新日期：2009-10-01 00:00:00
abstract：:Here we review the present state of structural and functional studies of the Sac10b protein family, a class of highly conserved 10 kDa nucleic acid-binding proteins in archaea. Based on biochemical and structural studies, these proteins were originally assigned a role in the structural organization of chromatin; Sac10...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/138920312800785067
更新日期：2012-05-01 00:00:00
abstract：:Prediction of protein domain boundaries is an important step for the prediction of three-dimensional structure. The simple method PDP has been elaborated for prediction of the number and position of domain boundaries in multi-domain proteins by use of amino acid sequence alone. The method uses an optimized scale based...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/138920307780363460
更新日期：2007-04-01 00:00:00
abstract：:The number of protein folds in nature is limited, thus is not surprising that proteins with the same fold are able to exert different functions. The cysteine protease inhibitors that adopt an immunoglobulin- like fold (Ig-ICPs) are inhibitors encoded in bacteria and protozoan parasites. Structural studies indicate tha...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/1389203717666160813163837
更新日期：2017-01-01 00:00:00
abstract：:Intestines are not only major organs for nutrient digestion and absorption, but are also the largest immune organ in pigs. They are essential for maintaining the health and growth of piglets. Fatty acids, including short-chain fatty acids, medium-chain fatty acids, and long-chain polyunsaturated fatty acids, are impor...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/1389203720666190514120023
更新日期：2019-01-01 00:00:00
abstract：:The Mastermind-like (MAML) proteins are transcriptional coactivators for Notch signaling, an evolutionarily conserved pathway that plays several key roles in development and in human disease. The MAML family contains MAML1, MAML2, and MAML3. More recently, MAML1 has been shown to function as a coactivator for the tumo...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/138920309789630543
更新日期：2009-12-01 00:00:00
abstract：:Glutathione (GSH or reduced glutathione) is a tripeptide of gamma-Glutamyl-cysteinylglycine and the predominant intracellular antioxidant in many organisms including humans. GSH and associated enzymes are controlled by a transcription factor-nuclear factor-2 related erythroid factor-2 (Nrf2). In cellular milieu, GSH p...
journal_title：Current protein & peptide science
pub_type： 杂志文章
doi：10.2174/1389203720666190206130003
更新日期：2019-01-01 00:00:00
abstract：:Glucagon-like peptide 2 (GLP-2) is a newly discovered gastrointestinal peptide with 33% sequence homology to glucagon. GLP-2 has attracted interest because of its potent intestinotrophic endocrine/paracrine actions. The peptide, consisting of 33-amino-acid, results from expression of the glucagon gene in the enteroend...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/1389203043486946
更新日期：2004-02-01 00:00:00
abstract：:CGRP and adrenomedullin [AM] are peptides that have a number of physiological effects, including vasodilation, through the activation of a shared GPCR, the family B calcitonin receptor-like receptor [CLR]. Specificity to each ligand is conferred through the unusual association of CLR with a single transmembrane access...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/13892037113149990053
更新日期：2013-08-01 00:00:00
abstract：:Angina pectoris, associated with coronary artery disease, a cardiovascular disease where, pain is caused by adverse oxygen supply in myocardium, resulting in contractility and discomfort in chest. Inflammasomes, triggered by stimuli due to infection and cellular stress have identified to play a vital role in the progr...
journal_title：Current protein & peptide science
pub_type： 杂志文章
doi：10.2174/1389203721999201208200242
更新日期：2020-12-08 00:00:00
abstract：:The complement system is a major effector arm of the immune defense contributing to the destruction of invading pathogens. There are three possible routes of complement cascade activation: the classical, the alternative and the lectin pathways. The activation of the classical and lectin pathways is initiated by supram...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/1389203013381242
更新日期：2001-03-01 00:00:00
abstract：:Adipose tissue is not only a tissue where energy is stored but is also involved in regulating several body functions such as appetite and energy expenditure via its endocrine activity. Moreover, it thereby modulates complex processes like reproduction, inflammation and immune response. The products secreted from adipo...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/1389203715666140221123105
更新日期：2014-03-01 00:00:00
abstract：:Naturally occurring protease inhibitors (PI) of the Bowman-Birk type constitute a major PI family in cereal and legume seeds. The family name is derived from the names of the two investigators who characterised the first inhibitor of this type, the Bowman-Birk inhibitor from soybean (BBI). These proteins have the capa...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/138920306777452349
更新日期：2006-06-01 00:00:00
abstract：:Skeletal muscle, the main protein reservoir in the body, is a tissue that exhibits high plasticity when exposed to changes. Muscle proteins can be mobilized into free amino acids when skeletal muscle wasting occurs, a process called skeletal muscle atrophy. This wasting is an important systemic or local manifestation ...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/138920312803582933
更新日期：2012-09-01 00:00:00
abstract：:The interactions of ligands with biomacromolecules play a fundamental role in almost all bioprocesses occuring in living organisms. The binding of ligands can cause the conformational changes of biomacromolecules, possibly affecting their physiological functions. The interactions of ligands with biomacromolecules are ...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/1389203717666160421152301
更新日期：2017-01-01 00:00:00
abstract：:The majority of tRNA studies has focused on tRNA molecules as pivotal player in the fundamental process of protein synthesis. Mounting studies have unveiled further functions for tRNA beyond protein synthesis, including non-ribosomal amino acid transfer, and regulation of targeted proteolysis. Post-translational N-ter...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/1389203719666180809113122
更新日期：2018-01-01 00:00:00
abstract：:Significant differences in function have been observed among lectins structurally similar to concanavalin A, but their high homology with this widely used lectin has kept them in obscurity. The observation of large differences in the potency of many of these Diocleinae lectins as stimulators of Interferon-g production...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/1389203013381152
更新日期：2001-06-01 00:00:00
abstract：:Dietary protein from fermented cottonseed meal (FCSM), widely used in poultry diets in China, had regulating effects on lipid metabolism. To understand the effects of FCSM on lipid metabolism in broilers, we analyzed the biochemical indexes, enzyme activity, hormone level and metabolites in serum responses to FCSM int...
journal_title：Current protein & peptide science
pub_type： 杂志文章
doi：10.2174/1389203721666200203152643
更新日期：2020-01-01 00:00:00
abstract：:Our understanding of the process of translation has progressed rapidly since the availability of highly resolved structures for the ribosome. A wealth of information has emerged in terms of both RNA and protein structure and the interplay between them. This has prompted us to revisit the astonishing "treasure trove" o...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/1389203023380846
更新日期：2002-02-01 00:00:00
abstract：:Evidence is accumulating that small open reading frames (sORF, <100 codons) play key roles in many important biological processes. Yet, they are generally ignored in gene annotation despite they are far more abundant than the genes with more than 100 codons. Here, we demonstrate that popular homolog search and codon-i...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/138920311796957667
更新日期：2011-09-01 00:00:00
abstract：:Tribbles homolog 3 (TRIB3) is a mammalian gene that is upregulated in response to several types of cell death-inducing cellular stress. The TRIB3 protein is a pseudokinase, a protein kinase-like scaffold with impaired catalytic activity. However, research has revealed it to be prolific at forming protein- protein inte...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/1389203718666170406124547
更新日期：2017-01-01 00:00:00
abstract：:Structural and theoretical analyses of proteins are central to the understanding of complex molecular mechanisms and are fundamental to the drug discovery process. Computational techniques yield useful insights into an ever-wider range of biomolecular systems. Protein three-dimensional structures and molecular functio...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/1389203023380657
更新日期：2002-06-01 00:00:00
abstract：:Membrane proteins play important roles in signal transduction across the cell membrane. Structural information for the membrane proteins is still limited due to many technical challenges. Membrane proteins containing a single α- helical transmembrane (TM) domain are very important in several pathways. Solution NMR spe...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/138920312803582979
更新日期：2012-09-01 00:00:00
abstract：:Toll-like receptors (TLRs) are type I transmembrane signaling molecules that are expressed in cells of the innate immune system. In these cells, TLRs function as pattern recognition receptors (PRR) that recognize specific molecular patterns derived from microorganisms. Upon activation, TLRs trigger a cascade of intrac...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/1389203711314010006
更新日期：2013-02-01 00:00:00
abstract：:Structure based drug designing is now a popular technique used for increasing the speed of drug designing process. This was made possible by the availability of many protein structures which helped in developing tools to understand the structure function relationships, automated docking and virtual screening. Knowledg...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/138920307781369454
更新日期：2007-08-01 00:00:00
abstract：:Secondary structure elements often mediate protein-protein interactions. Despite their low abundance in folded proteins, polyproline II (PPII) and its variant, the triple helix, are frequently involved in protein-protein interactions, likely due to their peculiar propensity to be solvent-exposed. We here review the ro...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/138920312804871157
更新日期：2012-12-01 00:00:00
abstract：:To defend themselves from attack by pathogens, plants can rely only on their innate defense systems. Defensins are antimicrobial peptides that contribute to plant immunity by displaying a direct cidal activity against various pathogens, some of which are responsible for plant diseases. These determine a significant de...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
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更新日期：2010-05-01 00:00:00
abstract：:Poly-N-acetyllactosamine structures occur in mammalian glycoproteins in both N- and O-linked glycans. They represent a backbone for additional modifications by fucosyltransferases, sialyltransferases and sulfotransferases. These glycans have been suggested to be involved in biospecific interactions with selectins and ...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/1389203033380304
更新日期：2003-02-01 00:00:00
abstract：:Serine proteinases fulfill and facilitate a broad spectrum of biological processes. They are held in check by different specific inhibitors. This delicate balance can be disturbed by genetic defects or exogenous influences and has been shown as the underlying or promoting cause for a large number of different diseases...
journal_title：Current protein & peptide science
pub_type： 杂志文章,评审
doi：10.2174/1389203054065374
更新日期：2005-06-01 00:00:00
