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Protein Science : a Publication of the... Nov 2020PAINT (points accumulation for imaging in nanoscale topography) refers to methods that achieve the sparse temporal labeling required for super-resolution imaging by... (Review)
Review
PAINT (points accumulation for imaging in nanoscale topography) refers to methods that achieve the sparse temporal labeling required for super-resolution imaging by using transient interactions between a biomolecule of interest and a fluorophore. There have been a variety of different implementations of this method since it was first described in 2006. Recent papers illustrate how transient peptide-protein interactions, rather than small molecule binding or DNA oligonucleotide duplex formation, can be employed to perform PAINT-based single molecule localization microscopy (SMLM). We discuss the different approaches to PAINT using peptide and protein interactions, and their applications in vitro and in vivo. We highlight the important parameters to consider when selecting suitable peptide-protein interaction pairs for such studies. We also note the opportunities for protein scientists to apply their expertise in guiding the choice of peptide and protein pairs that are used. Finally, we discuss the potential for expanding super-resolution imaging methods based on transient peptide-protein interactions, including the development of simultaneous multicolor imaging of multiple proteins and the study of very high and very low abundance proteins in live cells.
Topics: Peptides; Protein Interaction Maps; Proteins; Single Molecule Imaging
PubMed: 32949055
DOI: 10.1002/pro.3953 -
Molecules (Basel, Switzerland) Oct 2017Cyclodipeptides (CDP) represent a diverse family of small, highly stable, cyclic peptides that are produced as secondary functional metabolites or side products of... (Review)
Review
Cyclodipeptides (CDP) represent a diverse family of small, highly stable, cyclic peptides that are produced as secondary functional metabolites or side products of protein metabolism by bacteria, fungi, and animals. They are widespread in nature, and exhibit a broad variety of biological and pharmacological activities. CDP synthases (CDPSs) and non-ribosomal peptide synthetases (NRPSs) catalyze the biosynthesis of the CDP core structure, which is further modified by tailoring enzymes often associated with CDP biosynthetic gene clusters. In this review, we provide a comprehensive summary of CDP biosynthetic pathways and modifying enzymes. We also discuss the biological properties of some known CDPs and their possible applications in metabolic engineering.
Topics: Biosynthetic Pathways; Dipeptides; Peptides, Cyclic
PubMed: 29065531
DOI: 10.3390/molecules22101796 -
Molecular Cancer Sep 2018In contrast to normal cells, which use the aerobic oxidation of glucose as their main energy production method, cancer cells prefer to use anaerobic glycolysis to... (Review)
Review
In contrast to normal cells, which use the aerobic oxidation of glucose as their main energy production method, cancer cells prefer to use anaerobic glycolysis to maintain their growth and survival, even under normoxic conditions. Such tumor cell metabolic reprogramming is regulated by factors such as hypoxia and the tumor microenvironment. In addition, dysregulation of certain signaling pathways also contributes to cancer metabolic reprogramming. Among them, the Hippo signaling pathway is a highly conserved tumor suppressor pathway. The core oncosuppressive kinase cascade of Hippo pathway inhibits the nuclear transcriptional co-activators YAP and TAZ, which are the downstream effectors of Hippo pathway and oncogenic factors in many solid cancers. YAP/TAZ function as key nodes of multiple signaling pathways and play multiple regulatory roles in cancer cells. However, their roles in cancer metabolic reprograming are less clear. In the present review, we examine progress in research into the regulatory mechanisms of YAP/TAZ on glucose metabolism, fatty acid metabolism, mevalonate metabolism, and glutamine metabolism in cancer cells. Determining the roles of YAP/TAZ in tumor energy metabolism, particularly in relation to the tumor microenvironment, will provide new strategies and targets for the selective therapy of metabolism-related cancers.
Topics: Cell Cycle Proteins; Cell Hypoxia; Energy Metabolism; Gluconeogenesis; Glycolysis; Humans; Intracellular Signaling Peptides and Proteins; Neoplasms; Nuclear Proteins; Signal Transduction; Trans-Activators; Transcription Factors; Transcriptional Coactivator with PDZ-Binding Motif Proteins; Tumor Microenvironment
PubMed: 30176928
DOI: 10.1186/s12943-018-0882-1 -
Srpski Arhiv Za Celokupno Lekarstvo 2014Research on the renin-angiotensin system (RAS) has contributed significantly to advances in understanding cardiovascular and renal homeostasis and to the treatment of... (Review)
Review
Research on the renin-angiotensin system (RAS) has contributed significantly to advances in understanding cardiovascular and renal homeostasis and to the treatment of cardiovascular diseases. This review offers a brief history of the RAS with an overview of its major components and their functions, as well as blockers of the RAS, their clinical usage and current research that targets various components of the RAS. Because angiotensin-converting enzyme (ACE) metabolizes two biologically active peptides, one in the kallikrein-kinin system (KKS) and one in the RAS, it is the essential connection between the two systems. ACE releases very powerful hypertensive agent, angiotensin II and also inactivates strong hypotensive peptide, bradykinin. Inhibition of ACE thus has a dual effect, resulting in decreased angiotensin II and increased bradykinin. We described the KKS as well.
Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Guinea Pigs; Humans; Kallikrein-Kinin System; Peptidyl-Dipeptidase A; Renin-Angiotensin System
PubMed: 25731011
DOI: 10.2298/sarh1412756i -
Angewandte Chemie (International Ed. in... May 2021Proteolysis of proteins and peptides is involved in the infection of cells by enveloped viruses and also in the invasion and spread of cancer cells. Shutting down...
Proteolysis of proteins and peptides is involved in the infection of cells by enveloped viruses and also in the invasion and spread of cancer cells. Shutting down broad-specificity proteases, however, is problematic because normal functions by these proteases will be affected. Herein, nanoparticle receptors were prepared from molecular imprinting for complex biological peptides. Their strong and selective binding enabled them to protect their targeted sequences from proteolysis in aqueous solution at stoichiometric amounts. Generality of the method was demonstrated by the protection of hydrophobic and hydrophilic peptides from different proteases, selective protection of a segment of a long peptide, and selective protection of a targeted peptide in a mixture. Most interestingly, two receptors targeting different parts of a long peptide could work in cooperation to protect the overall sequence, highlighting the versatility of the method.
Topics: Peptide Hydrolases; Peptides; Proteolysis
PubMed: 33725413
DOI: 10.1002/anie.202102148 -
Clinical Epigenetics Jul 2019Peptides originating from different sources (endogenous, food derived, environmental, and synthetic) are able to influence different aspects of epigenetic regulation.... (Review)
Review
Peptides originating from different sources (endogenous, food derived, environmental, and synthetic) are able to influence different aspects of epigenetic regulation. Endogenous short peptides, resulting from proteolytic cleavage of proteins or upon translation of non-annotated out of frame transcripts, can block DNA methylation and hereby regulate gene expression. Peptides entering the body by digestion of food-related proteins can modulate DNA methylation and/or histone acetylation while environmental peptides, synthesized by bacteria, fungi, and marine sponges, mainly inhibit histone deacetylation. In addition, synthetic peptides that reverse or inhibit different epigenetic modifications of both histones and the DNA can be developed as well. Next to these DNA and histone modifications, peptides can also influence the expression of non-coding RNAs such as lncRNAs and the maturation of miRNAs.Seen the advantages over small molecules, the development of peptide therapeutics is an interesting approach to treat diseases with a strong epigenetic basis like cancer and Alzheimer's disease. To date, only a limited number of drugs with a proven epigenetic mechanism of action have been approved by the FDA of which two (romidepsin and nesiritide) are peptides. A large knowledge gap concerning epigenetic effects of peptides is present, and this class of molecules deserves more attention in the development as epigenetic modulators. In addition, none of the currently approved peptide drugs are under investigation for their potential effects on epigenetics, hampering drug repositioning of these peptides to other indications with an epigenetic etiology.
Topics: Acetylation; DNA Methylation; Epigenesis, Genetic; Histones; Humans; Peptides
PubMed: 31300053
DOI: 10.1186/s13148-019-0700-7 -
Journal of Proteome Research Aug 2022Virtual screening of protein-protein and protein-peptide interactions is a challenging task that directly impacts the processes of hit identification and hit-to-lead...
Virtual screening of protein-protein and protein-peptide interactions is a challenging task that directly impacts the processes of hit identification and hit-to-lead optimization in drug design projects involving peptide-based pharmaceuticals. Although several screening tools designed to predict the binding affinity of protein-protein complexes have been proposed, methods specifically developed to predict protein-peptide binding affinity are comparatively scarce. Frequently, predictors trained to score the affinity of small molecules are used for peptides indistinctively, despite the larger complexity and heterogeneity of interactions rendered by peptide binders. To address this issue, we introduce PPI-Affinity, a tool that leverages support vector machine (SVM) predictors of binding affinity to screen datasets of protein-protein and protein-peptide complexes, as well as to generate and rank mutants of a given structure. The performance of the SVM models was assessed on four benchmark datasets, which include protein-protein and protein-peptide binding affinity data. In addition, we evaluated our model on a set of mutants of EPI-X4, an endogenous peptide inhibitor of the chemokine receptor CXCR4, and on complexes of the serine proteases HTRA1 and HTRA3 with peptides. PPI-Affinity is freely accessible at https://protdcal.zmb.uni-due.de/PPIAffinity.
Topics: Drug Design; Peptides; Protein Binding; Proteins; Support Vector Machine
PubMed: 35654412
DOI: 10.1021/acs.jproteome.2c00020 -
Biochimica Et Biophysica Acta Nov 2004This review is focused on peptide molecules which exhibit a limited solubility in the aqueous phase and bind to the lipid membrane from the aqueous medium. Surface... (Review)
Review
This review is focused on peptide molecules which exhibit a limited solubility in the aqueous phase and bind to the lipid membrane from the aqueous medium. Surface adsorption, membrane insertion, and specific binding are usually accompanied by changes in the heat content of the system and can be measured conveniently with isothermal titration calorimetry, avoiding the necessity of peptide labeling. The driving forces for peptide adsorption and binding are hydrophobicity, electrostatics, and hydrogen bonding. An exclusively hydrophobic interaction is exemplified by the immunosuppressant drug cyclosporine A. Its insertion into the membrane can be described by a simple partition equilibrium X(b)=K(0)C(eq). If peptide and membrane are both charged, electrostatic interactions are dominant leading to nonlinear binding curves. The concentration of the peptide near the membrane interface can then be much larger than its bulk concentration. Electrostatic effects must be accounted for by means of the Gouy-Chapman theory before conventional binding models can be applied. A small number of peptides and proteins bind with very high affinity to a specific lipid species only. This is illustrated for the lantibiotic cinnamycin (Ro 09-0198) which forms a 1:1 complex with phosphatidyethanolamine with a binding constant of 10(8) M(-1). Membrane adsorption and insertion can be accompanied by conformational transitions facilitated, in part, by hydrogen bonding mechanisms. The two membrane-induced conformational changes to be discussed are the random coil-to-alpha-helix transition of amphipathic peptides and the random coil-to-beta-structure transition of Alzheimer peptides.
Topics: Membrane Lipids; Membrane Proteins; Peptides; Protein Binding; Protein Conformation; Thermodynamics
PubMed: 15519307
DOI: 10.1016/j.bbamem.2004.08.004 -
Frontiers in Endocrinology 2021More than 35 years have passed since the identification of neuromedin U (NMU). Dozens of publications have been devoted to its physiological role in the organism, which... (Review)
Review
More than 35 years have passed since the identification of neuromedin U (NMU). Dozens of publications have been devoted to its physiological role in the organism, which have provided insight into its occurrence in the body, its synthesis and mechanism of action at the cellular level. Two G protein-coupled receptors (GPCRs) have been identified, with NMUR1 distributed mainly peripherally and NMUR2 predominantly centrally. Recognition of the role of NMU in the control of energy homeostasis of the body has greatly increased interest in this neuromedin. In 2005 a second, structurally related peptide, neuromedin S (NMS) was identified. The expression of NMS is more restricted, it is predominantly found in the central nervous system. In recent years, further peptides related to NMU and NMS have been identified. These are neuromedin U precursor related peptide (NURP) and neuromedin S precursor related peptide (NSRP), which also exert biological effects without acting NMUR1, or NMUR2. This observation suggests the presence of another, as yet unrecognized receptor. Another unresolved issue within the NMU/NMS system is the differences in the effects of various NMU isoforms on diverse cell lines. It seems that development of highly specific NMUR1 and NMUR2 receptor antagonists would allow for a more detailed understanding of the mechanisms of action of NMU/NMS and related peptides in the body. They could form the basis for attempts to use such compounds in the treatment of disorders, for example, metabolic disorders, circadian rhythm, stress, etc.
Topics: Animals; Circadian Rhythm; Energy Metabolism; Homeostasis; Humans; Metabolic Diseases; Neuropeptides
PubMed: 34276571
DOI: 10.3389/fendo.2021.713961 -
Organic & Biomolecular Chemistry Jan 2021DNAzymes were previously identified by in vitro selection for a variety of chemical reactions, including several biologically relevant peptide modifications. However,...
DNAzymes were previously identified by in vitro selection for a variety of chemical reactions, including several biologically relevant peptide modifications. However, finding DNAzymes for peptide lysine acylation is a substantial challenge. By using suitably reactive aryl ester acyl donors as the electrophiles, here we used in vitro selection to identify DNAzymes that acylate amines, including lysine side chains of DNA-anchored peptides. Some of the DNAzymes can transfer a small glutaryl group to an amino group. These results expand the scope of DNAzyme catalysis and suggest the future broader applicability of DNAzymes for sequence-selective lysine acylation of peptide and protein substrates.
Topics: Acylation; Amines; Biocatalysis; DNA, Catalytic; Lysine; Peptides
PubMed: 33150349
DOI: 10.1039/d0ob02015j