Naturally occurring low-molecular-weight peptides from the blowfly Phormia regina.
Ontology highlight
ABSTRACT:
SUBMITTER: Bodnaryk RP
PROVIDER: S-EPMC1187453 | biostudies-other | 1968 Dec
REPOSITORIES: biostudies-other
Similar Datasets
Project description:α,β-Dehydroamino acids are naturally occurring non-coded amino acids, found primarily in peptides. The review focuses on the type of α,β-dehydroamino acids, the structure of dehydropeptides, the source of their origin and bioactivity. Dehydropeptides are isolated primarily from bacteria and less often from fungi, marine invertebrates or even higher plants. They reveal mainly antibiotic, antifungal, antitumour, and phytotoxic activity. More than 60 different structures were classified, which often cover broad families of peptides. 37 different structural units containing the α,β-dehydroamino acid residues were shown including various side chains, Z and E isomers, and main modifications: methylation of peptide bond as well as the introduction of ester group and heterocycle ring. The collected data show the relation between the structure and bioactivity. This allows the activity of compounds, which were not studied in this field, but which belong to a larger peptide family to be predicted. A few examples show that the type of the geometrical isomer of the α,β-dehydroamino acid residue can be important or even crucial for biological activity.
| S-EPMC4282715 | biostudies-literature
Project description:To assess normal and pathological peptidomic changes that may lead to an improved understanding of molecular mechanisms underlying ageing, urinarypeptidomes of 1227 healthy and 10333 diseased individuals between 20 and 86 years of age were investigated. The diseases thereby comprised diabetes mellitus, renal and cardiovascular diseases. Using age as a continuous variable, 116 peptides were identified that significantly (p < 0.05; |?|?0.2) correlated with age in the healthy cohort. The same approach was applied to the diseased cohort. Upon comparison of the peptide patterns of the two cohorts 112 common age-correlated peptides were identified. These 112 peptides predominantly originated from collagen, uromodulin and fibrinogen. While most fibrillar and basement membrane collagen fragments showed a decreased age-related excretion, uromodulin, beta-2-microglobulin and fibrinogen fragments showed an increase. Peptide-based in silico protease analysis was performed and 32 proteases, including matrix metalloproteinases and cathepsins, were predicted to be involved in ageing. Identified peptides, predicted proteases and patient information were combined in a systems biology pathway analysis to identify molecular pathways associated with normal and/or pathological ageing. While perturbations in collagen homeostasis, trafficking of toll-like receptors and endosomal pathways were commonly identified, degradation of insulin-like growth factor-binding proteins was uniquely identified in pathological ageing.
| S-EPMC4741439 | biostudies-literature
Project description:To date, cone snail toxins ("conotoxins") are of great interest in the pursuit of novel subtype-selective modulators of voltage-gated sodium channels (Na(v)s). Na(v)s participate in a wide range of electrophysiological processes. Consequently, their malfunctioning has been associated with numerous diseases. The development of subtype-selective modulators of Na(v)s remains highly important in the treatment of such disorders. In current research, a series of novel, synthetic, and bioactive compounds were designed based on two naturally occurring μ-conotoxins that target Na(v)s. The initial designed peptide contains solely 13 amino acids and was therefore named "Mini peptide." It was derived from the μ-conotoxins KIIIA and BuIIIC. Based on this Mini peptide, 10 analogues were subsequently developed, comprising 12-16 amino acids with two disulfide bridges. Following appropriate folding and mass verification, blocking effects on Na(v)s were investigated. The most promising compound established an IC(50) of 34.1 ± 0.01 nM (R2-Midi on Na(v)1.2). An NMR structure of one of our most promising compounds was determined. Surprisingly, this structure does not reveal an α-helix. We prove that it is possible to design small peptides based on known pharmacophores of μ-conotoxins without losing their potency and selectivity. These data can provide crucial material for further development of conotoxin-based therapeutics.
| S-EPMC3438967 | biostudies-literature
Project description:In contrast to protein O-phosphorylation, studying the function of the less frequent N- and S-phosphorylation events have lagged behind because they have chemical features that prevent their manipulation through standard synthetic and analytical methods. Here we report on the development of a chemoselective synthetic method to phosphorylate Cys side-chains in unprotected peptides. This approach makes use of a reaction between nucleophilic phosphites and electrophilic disulfides accessible by standard methods. We achieve the stereochemically defined phosphorylation of a Cys residue and verify the modification using electron-transfer higher-energy dissociation (EThcD) mass spectrometry. To demonstrate the use of the approach in resolving biological questions, we identify an endogenous Cys phosphorylation site in IICB(Glc), which is known to be involved in the carbohydrate uptake from the bacterial phosphotransferase system (PTS). This new chemical and analytical approach finally allows further investigating the functions and significance of Cys phosphorylation in a wide range of crucial cellular processes.
| S-EPMC5025809 | biostudies-other
Project description:The impact that β-arrestin proteins have on G protein-coupled receptor trafficking, signaling and physiological behavior has gained much appreciation over the past decade. A number of studies have attributed the side effects associated with the use of naturally occurring and synthetic opioids, such as respiratory depression and constipation, to excessive recruitment of β-arrestin. These findings have led to the development of biased opioid small molecule agonists that do not recruit β-arrestin, activating only the canonical G protein pathway. Similar G protein-biased small molecule opioids have been found to occur in nature, particularly within kratom, and opioids within salvia have served as a template for the synthesis of other G protein-biased opioids. Here, we present the first report of naturally occurring peptides that selectively activate G protein signaling pathways at δ opioid receptors, but with minimal β-arrestin recruitment. Specifically, we find that rubiscolin peptides, which are produced as cleavage products of the plant protein rubisco, bind to and activate G protein signaling at δ opioid receptors. However, unlike the naturally occurring δ opioid peptides leu-enkephalin and deltorphin II, the rubiscolin peptides only very weakly recruit β-arrestin 2 and have undetectable recruitment of β-arrestin 1 at the δ opioid receptor.
| S-EPMC6421079 | biostudies-literature
Project description:Because of its availability, ease of collection, and correlation with physiology and pathology, urine is an attractive source for clinical proteomics/peptidomics. However, the lack of comparable data sets from large cohorts has greatly hindered the development of clinical proteomics. Here, we report the establishment of a reproducible, high resolution method for peptidome analysis of naturally occurring human urinary peptides and proteins, ranging from 800 to 17,000 Da, using samples from 3,600 individuals analyzed by capillary electrophoresis coupled to MS. All processed data were deposited in an Structured Query Language (SQL) database. This database currently contains 5,010 relevant unique urinary peptides that serve as a pool of potential classifiers for diagnosis and monitoring of various diseases. As an example, by using this source of information, we were able to define urinary peptide biomarkers for chronic kidney diseases, allowing diagnosis of these diseases with high accuracy. Application of the chronic kidney disease-specific biomarker set to an independent test cohort in the subsequent replication phase resulted in 85.5% sensitivity and 100% specificity. These results indicate the potential usefulness of capillary electrophoresis coupled to MS for clinical applications in the analysis of naturally occurring urinary peptides.
| S-EPMC2984241 | biostudies-literature
Project description:The incidence of hepatocellular carcinoma (HCC) in the United States is increasing and the increase is projected to continue for several decades. The overall survival of HCC patients is poor and treatments are not effective in part because most of the diagnoses come at a late stage. The development of new markers for detection of HCC would significantly improve patient prognosis. This paper describes identification of candidate markers previously reported in our serologic study of an Egyptian population by quantitative comparison of matrix assisted laser desorption ionization time of flight (MALDI-TOF) mass spectra. To identify these marker candidates, we performed LC-MS/MS sequencing that identified nine native peptides associated with HCC, including two reported previously. Four truncations of N terminus of complement C3f and a fibrinopeptide increased in control sera; two complement C4alpha peptides, a zyxin peptide, and a coagulation factor XIII peptide increased in cancer patient sera. We have also identified increased biliverdin diglucuronide in the sera of cancer patients. These peptides could potentially serve as markers of HCC following additional validation studies; however, association of similar peptides with other diseases and cancers dictates a very cautious approach.
| S-EPMC3552294 | biostudies-literature
Project description:BackgroundImmunotherapy using checkpoint inhibitors, especially PD-1/PD-L1 inhibitors, has now evolved into the most promising therapy for cancer patients. However, most of these inhibitors are monoclonal antibodies, and their large size may limit their tumor penetration, leading to suboptimal efficacy. As a result, there has been a growing interest in developing low-molecular-weight checkpoint inhibitors.MethodsWe developed a novel biopanning strategy to discover small peptide-based anti-PD-L1 inhibitors. The affinity and specificity of the peptides to PD-L1 were examined using various assays. Three-dimensional (3D) spheroid penetration study was performed to determine the tumor penetration capability of the peptides. Anti-tumor activity of the peptides was evaluated in mice bearing CT26 tumor cells.ResultsWe discover several anti-PD-L1 peptide inhibitors to block PD-1/PD-L1 interaction. The peptides exhibit high affinity and specificity to human PD-L1 protein as well as PD-L1-overexpressing human cancer cells MDA-MB-231 and DU-145. Molecular docking studies indicate that the peptide CLP002 specifically binds to PD-L1 at the residues where PD-L1 interacts with PD-1. The peptide also blocks the CD80/PD-L1 interaction, which may further enhance the immune response of tumor-infiltrating T cells. Compared to antibody, the peptide CLP002 exhibits better tumor penetration in a 3D tumor spheroid model. The peptide CLP002 restores proliferation and prevents apoptosis of T cells that are co-cultured with cancer cells. The peptide CLP002 also inhibits tumor growth and increases survival of CT26 tumor-bearing mice.ConclusionsThis study demonstrated the feasibility of using phage display to discover small peptide-based checkpoint inhibitors. Our results also suggested that the anti-PD-L1 peptide represents a promising low-molecular-weight checkpoint inhibitor for cancer immunotherapy.
| S-EPMC6805442 | biostudies-literature
Project description:Previously, we reported the isolation of 10 vancomycin-resistant gram-positive anaerobic bacilli carrying the vanB ligase gene from nine hemodialysis patients (S. A. Ballard et al., Antimicrob. Agents Chemother. 49:77-81, 2005; T. P. Stinear et al., Lancet 357:855-856, 2001). In the present study, the molecular and evolutionary relationship of the vanB resistance element within these 10 anaerobes and two vancomycin-resistant Enterococcus faecium strains were examined. PCR analysis and nucleotide sequencing demonstrated that all 12 isolates carried the vanB operon associated with an element identical to Tn1549 and Tn5382 of Enterococcus. Restriction fragment length polymorphism analysis of the vanB operon in these isolates revealed two distinct patterns, and sequencing showed that minor base differences existed. PCR amplification of the joint region of a circular intermediate was demonstrated in nine of these organisms, a finding indicative of an ability to excise and circularize, an intermediate step in transposition and conjugative transfer. Southern hybridization with a vanB-vanX(B) probe suggests that there is one insert of the transposon in all isolates. Sequence analysis of the integration site revealed distinct sequences: the Tn1549/5382 element within E. faecium was inserted within the host chromosome, whereas nucleotide sequences surrounding the Tn1549/5382 element in the 10 anaerobes showed no significant homology to sequences in the GenBank database. We demonstrate considerable similarity between the Tn1549/5382 element identified in 10 anaerobe isolates with that found in enterococci. The homology and potential to transpose suggest a recent horizontal transfer event may have occurred. However, the original direction of transposition and the mechanism involved remains unknown.
| S-EPMC1087664 | biostudies-literature
Project description:Genetic, epidemiological and pharmacological data have led to the conclusion that antagonizing or inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces cardiovascular events. This clinical outcome is mainly related to the pivotal role of PCSK9 in controlling low-density lipoprotein (LDL) cholesterol levels. The absence of oral and affordable anti-PCSK9 medications has limited the beneficial effects of this new therapeutic option. A possible breakthrough in this field may come from the discovery of new naturally occurring PCSK9 inhibitors as a starting point for the development of oral, small molecules, to be used in combination with statins in order to increase the percentage of patients reaching their LDL-cholesterol target levels. In the present review, we have summarized the current knowledge on natural compounds or extracts that have shown an inhibitory effect on PCSK9, either in experimental or clinical settings. When available, the pharmacodynamic and pharmacokinetic profiles of the listed compounds are described.
| S-EPMC7284437 | biostudies-literature