scholarly journals Dual host-defence functions of SPLUNC2/PSP and synthetic peptides derived from the protein

2011 ◽  
Vol 39 (4) ◽  
pp. 1028-1032 ◽  
Author(s):  
Sven-Ulrik Gorr ◽  
Mahsa Abdolhosseini ◽  
Anuradha Shelar ◽  
Julie Sotsky
Keyword(s):  
Synthetic Peptides ◽  
Inhibitory Concentration ◽  
Secretory Protein ◽  
Plant Model ◽  
Lead Compounds ◽  
Parotid Secretory Protein ◽  
Anti Inflammatory ◽  
Role Based ◽  
Spread Of Infection ◽  
Lps Binding

PSP (parotid secretory protein)/SPLUNC2 (short palate, lung and nasal epithelium clone 2) is expressed in human salivary glands and saliva. The protein exists as an N-glycosylated and non-glycosylated form and both appear to induce agglutination of bacteria, a major antibacterial function for salivary proteins. Both forms of PSP/SPLUNC2 bind LPS (lipopolysaccharide), suggesting that the protein may also play an anti-inflammatory role. Based on the predicted structure of PSP/SPLUNC2 and the location of known antibacterial and anti-inflammatory peptides in BPI (bactericidal/permeability-increasing protein) and LBP (LPS-binding protein), we designed GL13NH2 and GL13K, synthetic peptides that capture these proposed functions of PSP/SPLUNC2. GL13NH3 agglutinates bacteria, leading to increased clearance by macrophages and reduced spread of infection in a plant model. GL13K kills bacteria with a minimal inhibitory concentration of 5–10 μg/ml, kills bacteria in biofilm and retains activity in 150 mM NaCl and 50% saliva. Both peptides block endotoxin action, but only GL13K appears to bind endotoxin. The peptides do not cause haemolysis, haemagglutination in serum, inhibit mammalian cell proliferation or induce an inflammatory response in macrophages. These results suggest that the GL13NH2 and the modified peptide GL13K capture the biological activity of PSP/SPLUNC2 and can serve as lead compounds for the development of novel antimicrobial and anti-inflammatory peptides.

Design and Validation of Anti-inflammatory Peptides from Human Parotid Secretory Protein

2005 ◽  
Vol 84 (2) ◽  
pp. 149-153 ◽  
Author(s):  
C. Geetha ◽  
S.G. Venkatesh ◽  
L. Bingle ◽  
C.D. Bingle ◽  
S.-U. Gorr
Keyword(s):  
Active Regions ◽  
Polymyxin B ◽  
Inhibitory Effect ◽  
Secretory Protein ◽  
Secretory Proteins ◽  
Cationic Peptides ◽  
Upper Airways ◽  
Raw 264.7 Macrophage Cells ◽  
Parotid Secretory Protein ◽  
Anti Inflammatory

Parotid secretory protein (PSP) and palate-lung-nasal epithelium clone (PLUNC) are novel secretory proteins that are expressed in the oral cavity and upper airways. Both proteins are related to bactericidal/permeability increasing protein (BPI). Cationic peptides derived from BPI exhibit anti-inflammatory activity. To test if PSP (C20orf70 gene product) also contains anti-inflammatory peptides, we designed 3 cationic peptides based on the predicted structure of PSP and known active regions of BPI. Each peptide inhibited the lipopolysaccharide (LPS)-stimulated secretion of TNFα from RAW 264.7 macrophage cells. At 200 μg/mL, the peptide GK-7 exhibited inhibition similar to that achieved with 10 μg/mL of polymyxin B. PSP peptides directly inhibited the binding of LPS to LPS-binding protein. The cationic peptide Substance P had no inhibitory effect in these assays, confirming the specificity of the PSP peptides. These findings suggest that PSP peptides can serve as templates for the design of novel anti-inflammatory peptides.

Antimicrobial Peptides and their Multiple Effects at Sub-Inhibitory Concentrations

2020 ◽  
Vol 20 (14) ◽  
pp. 1264-1273 ◽  
Author(s):  
Bruno Casciaro ◽  
Floriana Cappiello ◽  
Walter Verrusio ◽  
Mauro Cacciafesta ◽  
Maria Luisa Mangoni
Keyword(s):  
Antimicrobial Peptides ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Lead Compounds ◽  
Bacterial Pathogenicity ◽  
Growth Inhibitory ◽  
Resistant Strains ◽  
Conventional Antibiotics

The frequent occurrence of multidrug-resistant strains to conventional antimicrobials has led to a clear decline in antibiotic therapies. Therefore, new molecules with different mechanisms of action are extremely necessary. Due to their unique properties, antimicrobial peptides (AMPs) represent a valid alternative to conventional antibiotics and many of them have been characterized for their activity and cytotoxicity. However, the effects that these peptides cause at concentrations below the minimum growth inhibitory concentration (MIC) have yet to be fully analyzed along with the underlying molecular mechanism. In this mini-review, the ability of AMPs to synergize with different antibiotic classes or different natural compounds is examined. Furthermore, data on microbial resistance induction are reported to highlight the importance of antibiotic resistance in the fight against infections. Finally, the effects that sub-MIC levels of AMPs can have on the bacterial pathogenicity are summarized while showing how signaling pathways can be valid therapeutic targets for the treatment of infectious diseases. All these aspects support the high potential of AMPs as lead compounds for the development of new drugs with antibacterial and immunomodulatory activities.

Bioactive potential of culturable fungal endophytes isolated from leaf of Catharanthus roseus (L.) G. Don

2021 ◽  
Vol 21 ◽  
Author(s):  
Sucheta Singh ◽  
Surjeet Verma ◽  
Dharmendra Kumar Yadav ◽  
Anant Kumar ◽  
Rekha Tyagi ◽  
...  
Keyword(s):  
Catharanthus Roseus ◽  
Crude Extract ◽  
Inhibitory Concentration ◽  
Efflux Pump ◽  
Fungal Endophytes ◽  
Bacterial Pathogen ◽  
Bioactive Compound ◽  
Major Constituent ◽  
Anti Inflammatory ◽  
Bioactive Potential

Introduction: Endophyte is considered as a source of natural bioactive secondary metabolites that provides an array of bioactive lead compounds. The present study was aimed to determine the antimicrobial and anti-inflammatory potential of fungal endophytes isolated from Catharanthus roseus. Methods: A total of seven fungal endophytes crude extract were screened against bacterial pathogens. Of these, Curvularia geniculata CATDLF7 crude extract exhibited the most potent inhibitory activity against bacterial pathogen. Hence, CATDLF7 crude extract was subjected to the chromatographic separation. This purification leads to the isolation of six pure compounds (1PS - 6PS). Of these, 3PS was found to be a major constituent and most effective against clinical isolates of methicillin resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration (MIC) values ranging from 100 to 200 μg/ml. Based on the spectroscopic data, 3PS was characterized as α,β-dehydrocurvularin. This compound also showed synergistic interaction with norfloxacin, and reduced its MIC up to 32-folds with fractional inhibitory concentration index (FICI) of 0.09. Results: To understand the possible antibacterial mechanism of action, α,β-dehydrocurvularin alone (100 μg/ml) exhibited efflux pump inhibitory potential by 0.84 fold decreasing in ethidium bromide (EtBr) fluorescence. In addition, α,β-dehydrocurvularin inhibited inflammatory cytokines TNF-α and IL-6 production which is further validated by molecular docking score -4.921 and -5.641 respectively for understanding orientation and binding affinity. Conclusion: Overall the results highlighted to identifying bioactive compound α,β-dehydrocurvularin which could be used as an antimicrobial and anti-inflammatory agents.

scholarly journals The parotid secretory protein BPIFA2 is a salivary surfactant that affects lipopolysaccharide action

2020 ◽  
Vol 105 (8) ◽  
pp. 1280-1292
Author(s):  
Seshagiri Rao Nandula ◽  
Ian Huxford ◽  
Thomas T. Wheeler ◽  
Conrado Aparicio ◽  
Sven‐Ulrik Gorr
Keyword(s):  
Secretory Protein ◽  
Parotid Secretory Protein

Bovine parotid secretory protein: structure, expression and relatedness to other BPI (bactericidal/permeability-increasing protein)-like proteins

2003 ◽  
Vol 31 (4) ◽  
pp. 781-784 ◽  
Author(s):  
T.T. Wheeler ◽  
K. Hood ◽  
K. Oden ◽  
J. McCracken ◽  
C.A. Morris
Keyword(s):  
Minor Salivary Gland ◽  
Secretory Protein ◽  
Protein Family ◽  
Sequence Information ◽  
The Family ◽  
Salivary Gland Protein ◽  
Full Length Sequence ◽  
Parotid Secretory Protein ◽  
Restricted Pattern

Members of the family of BPI (bactericidal/permeability-increasing protein)-like proteins are as yet incompletely characterized, particularly in cattle, where full-length sequence information is available for only three of the 13 family members known from other species. Structural bioinformatic analyses incorporating bovine homologues of several members of the BPI-like protein family, including two forms of bovine parotid secretory protein (PSP), showed that this family is also present in cattle. Expression analyses of several members of the BPI-like protein family in cattle, including PSP (Bsp30), von Ebner's minor salivary gland protein (VEMSGP) and lung-specific X protein (LUNX), showed a restricted pattern of expression, consistent with earlier hypotheses that these proteins function in the innate immune response to bacteria. The possible role of bovine PSP in susceptibility to pasture bloat in cattle is discussed.

scholarly journals Synthesis, Characterization, and Antibacterial and Anti-Inflammatory Activities of New Pyrimidine and Thiophene Derivatives

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Siham Lahsasni ◽  
Dunya A. M. Al-Hemyari ◽  
Hazem A. Ghabbour ◽  
Yahia Nasser Mabkhoot ◽  
Fadilah S. Aleanizy ◽  
...  
Keyword(s):  
Nucleophilic Substitution ◽  
Phenyl Isothiocyanate ◽  
Standard Drug ◽  
Thiourea Derivatives ◽  
X Ray ◽  
X Ray Crystallography ◽  
Lead Compounds ◽  
Antimicrobial Studies ◽  
Thiophene Derivatives ◽  
Anti Inflammatory

Substituted[4,5]thieno[2,3-d]thiazolo[3,2-a]pyrimidin-5-one (3a–b) and pyrimidin-5(6H)-imine (3c–e) were synthesized via reaction of the starting compounds, ethyl 2-amino-substituted[b]thiophene-3-carboxylate (2a–c) and 2-amino-substituted [b]thiophene-3-carbonitrile (2d–f), respectively, with 2-bromothiazole. Synthesis of (bromo-substituted[b]thiophen-2-yl)alkanamide derivatives (4a–e) and thieno[2,3-d][1,3]oxazin-4-imine derivative (5) was accomplished via reaction of the starting compounds with bromoalkyl chloride through nucleophilic substitution; however, for the synthesis of compound 5, nucleophilic substitution was followed by nucleophilic addition to a nitrile group to form the oxazinimine ring. 1-(3-cyano-substituted[b]thiophen-2-yl)-3-(4-(trifluoromethyl)phenyl)thiourea derivatives (6a–c) were obtained via reaction of the starting compounds (2d–f) and 4-(trifluoromethyl phenyl)isothiocyanate. The lead compounds (2d–f) rapidly reacted with 4-(trifluoromethyl)benzaldehyde or 4-(2-pyridyl)benzaldehyde in acidic medium to yield compounds (7a–f) in large quantities. X-ray crystallography of compounds 4c and 7e confirmed their structures. Antimicrobial studies revealed that compound 6a was equally potent to ampicillin against Bacillus strains. Moreover, compounds 3e, 4d, and 6a possessed greater anti-inflammatory potency than that of the standard drug.

scholarly journals C-Terminal Amination of a Cationic Anti-Inflammatory Peptide Improves Bioavailability and Inhibitory Activity Against LPS-Induced Inflammation

2021 ◽  
Vol 11 ◽  
Author(s):  
Lulu Zhang ◽  
Xubiao Wei ◽  
Rijun Zhang ◽  
Matthew Koci ◽  
Dayong Si ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Cell Uptake ◽  
Inflammatory Activity ◽  
Myeloid Differentiation ◽  
Toll Like Receptor 4 ◽  
Native Peptides ◽  
Anti Inflammatory ◽  
Myeloid Differentiation Factor ◽  
Inflammatory Effect ◽  
Lps Binding

Lipopolysaccharide (LPS) has been implicated as a major cause of inflammation and an uncontrolled LPS response increases the risk of localized inflammation and sepsis. While some native peptides are helpful in the treatment of LPS-induced inflammation, the use of these peptides is limited due to their potential cytotoxicity and poor anti-inflammatory activity. Hybridization is an effective approach for overcoming this problem. In this study, a novel hybrid anti-inflammatory peptide that combines the active center of Cathelicidin 2 (CATH2) with thymopentin (TP5) was designed [CTP, CATH2 (1–13)-TP5]. CTP was found to have higher anti-inflammatory effects than its parental peptides through directly LPS neutralization. However, CTP scarcely inhibited the attachment of LPS to cell membranes or suppressed an established LPS-induced inflammation due to poor cellular uptake. The C-terminal amine modification of CTP (CTP-NH2) was then designed based on the hypothesis that C-terminal amidation can enhance the cell uptake by increasing the hydrophobicity of the peptide. Compared with CTP, CTP-NH2 showed enhanced anti-inflammatory activity and lower cytotoxicity. CTP-NH2 not only has strong LPS neutralizing activity, but also can significantly inhibit the LPS attachment and the intracellular inflammatory response. The intracellular anti-inflammatory effect of CTP-NH2 was associated with blocking of LPS binding to the Toll-like receptor 4-myeloid differentiation factor 2 complex and inhibiting the nuclear factor-kappa B pathway. In addition, the anti-inflammatory effect of CTP-NH2 was confirmed using a murine LPS-induced sepsis model. Collectively, these findings suggest that CTP-NH2 could be developed into a novel anti-inflammatory drug. This successful modification provides a design strategy to improve the cellular uptake and anti-inflammatory activity of peptide agents.

scholarly journals INHERITANCE OF A PAROTID SECRETORY PROTEIN IN MICE AND ITS USE IN DETERMINING SALIVARY AMYLASE QUANTITATIVE VARIANTS

Genetics ◽  
1980 ◽  
Vol 95 (1) ◽  
pp. 129-141
Author(s):  
David Owerbach ◽  
J Peter Hjorth
Keyword(s):  
Cyanogen Bromide ◽  
Inbred Strains ◽  
Secretory Protein ◽  
Major Protein ◽  
Chromosome 2 ◽  
Parotid Glands ◽  
Salivary Amylase ◽  
Inbred Strains Of Mice ◽  
Mendelian Factor ◽  
Parotid Secretory Protein

ABSTRACT Among inbred strains of mice, a major protein, PSP, produced and secreted by the parotid glands, shows variation in electrophoretic mobility and in the peptides produced by cyanogen bromide treatment. This variation is inherited as a single Mendelian factor with two alleles showing co-dominant expression. In genetic crosses, it segregates independently from the amylase complex and is closely linked to the agouti locus on chromosome 2. The protein ratios between amylase and PSP in saliva, obtained by scanning of electrophoretic gel separations, were found to reflect genetic differences in salivary amylase production in strains YBR/Cv and C3H/As.

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