scholarly journals Structure and Activity of a Selective Antibiofilm Peptide SK-24 Derived from the NMR Structure of Human Cathelicidin LL-37

2021 ◽  
Vol 14 (12) ◽  
pp. 1245
Author(s):  
Yingxia Zhang ◽  
Jayaram Lakshmaiah Narayana ◽  
Qianhui Wu ◽  
Xiangli Dang ◽  
Guangshun Wang
Keyword(s):  
Therapeutic Potential ◽  
Nmr Structure ◽  
Helical Conformation ◽  
Antibiofilm Activity ◽  
Hydrophobic Domain ◽  
Bacterial Membranes ◽  
Host Defense Peptide ◽  
Activity Spectrum ◽  
Coiled Helix ◽  
Structure And Activity

The deployment of the innate immune system in humans is essential to protect us from infection. Human cathelicidin LL-37 is a linear host defense peptide with both antimicrobial and immune modulatory properties. Despite years of studies of numerous peptides, SK-24, corresponding to the long hydrophobic domain (residues 9–32) in the anionic lipid-bound NMR structure of LL-37, has not been investigated. This study reports the structure and activity of SK-24. Interestingly, SK-24 is entirely helical (~100%) in phosphate buffer (PBS), more than LL-37 (84%), GI-20 (75%), and GF-17 (33%), while RI-10 and 17BIPHE2 are essentially randomly coiled (helix%: 7%–10%). These results imply an important role for the additional N-terminal amino acids (likely E16) of SK-24 in stabilizing the helical conformation in PBS. It is proposed herein that SK-24 contains the minimal sequence for effective oligomerization of LL-37. Superior to LL-37 and RI-10, SK-24 shows an antimicrobial activity spectrum comparable to the major antimicrobial peptides GF-17 and GI-20 by targeting bacterial membranes and forming a helical conformation. Like the engineered peptide 17BIPHE2, SK-24 has a stronger antibiofilm activity than LL-37, GI-20, and GF-17. Nevertheless, SK-24 is least hemolytic at 200 µM compared with LL-37 and its other peptides investigated herein. Combined, these results enabled us to appreciate the elegance of the long amphipathic helix SK-24 nature deploys within LL-37 for human antimicrobial defense. SK-24 may be a useful template of therapeutic potential.

scholarly journals Acylation of SC4 dodecapeptide increases bactericidal potency against Gram-positive bacteria, including drug-resistant strains

2004 ◽  
Vol 378 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Nathan A. LOCKWOOD ◽  
Judith R. HASEMAN ◽  
Matthew V. TIRRELL ◽  
Kevin H. MAYO
Keyword(s):  
Fatty Acid ◽  
Fluorescence Spectroscopy ◽  
Bactericidal Activity ◽  
Bacterial Cell ◽  
Membrane Surface ◽  
Peptide Amphiphiles ◽  
Helical Conformation ◽  
Gram Positive ◽  
Bacterial Membranes ◽  
Bactericidal Activities

We have conjugated dodecyl and octadecyl fatty acids to the N-terminus of SC4, a potently bactericidal, helix-forming peptide 12-mer (KLFKRHLKWKII), and examined the bactericidal activities of the resultant SC4 ‘peptide-amphiphile’ molecules. SC4 peptide-amphiphiles showed up to a 30-fold increase in bactericidal activity against Gram-positive strains (Staphylococcus aureus, Streptococcus pyogenes and Bacillus anthracis), including S. aureus strains resistant to conventional antibiotics, but little or no increase in bactericidal activity against Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Fatty acid conjugation improved endotoxin (lipopolysaccharide) neutralization by 3- to 6-fold. Although acylation somewhat increased lysis of human erythrocytes, it did not increase lysis of endothelial cells, and the haemolytic effects occurred at concentrations 10- to 100-fold higher than those required for bacterial cell lysis. For insight into the mechanism of action of SC4 peptide-amphiphiles, CD, NMR and fluorescence spectroscopy studies were performed in micelle and liposome models of eukaryotic and bacterial cell membranes. CD indicated that SC4 peptide-amphiphiles had the strongest helical tendencies in liposomes mimicking bacterial membranes, and strong membrane integration of the SC4 peptide-amphiphiles was observed using tryptophan fluorescence spectroscopy under these conditions; results that correlated with the increased bactericidal activities of SC4 peptide-amphiphiles. NMR structural analysis in micelles demonstrated that the two-thirds of the peptide closest to the fatty acid tail exhibited a helical conformation, with the positively-charged side of the amphipathic helix interacting more with the model membrane surface. These results indicate that conjugation of a fatty acid chain to the SC4 peptide enhances membrane interactions, stabilizes helical structure in the membrane-bound state and increases bactericidal potency.

scholarly journals NMR structure of the water soluble Aβ17–34 peptide

2014 ◽  
Vol 34 (6) ◽  
Author(s):  
Genadiy Fonar ◽  
Abraham O. Samson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nicotinic Acetylcholine Receptors ◽  
Neurodegenerative Disorder ◽  
Amyloid Β ◽  
Helical Structure ◽  
Nmr Structure ◽  
Water Soluble ◽  
Helical Conformation ◽  
Aβ Amyloid

Alzheimer's disease is the most common neurodegenerative disorder in the world. Its most significant symptoms are memory loss and decrease in cognition. Alzheimer's disease is characterized by aggregation of two proteins in the brain namely Aβ (amyloid β) and tau. Recent evidence suggests that the interaction of soluble Aβ with nAChR (nicotinic acetylcholine receptors) contributes to disease progression. In this study, we determine the NMR structure of an Aβ17–34 peptide solubilized by the addition of two glutamic acids at each terminus. Our results indicate that the Aβ peptide adopts an α-helical structure for residues 19–26 and 28–33. The α-helical structure is broken around residues S26, N27 and K28, which form a kink in the helical conformation. This α-helix was not described earlier in an aqueous solution without organic solvents, and at physiological conditions (pH 7). These data are in agreement with Aβ adopting an α-helical conformation in the membrane before polymerizing into amyloid β-sheets and provide insight into the intermediate state of Aβ in Alzheimer's disease.

scholarly journals Chrysin-Loaded Chitosan Nanoparticles Potentiates Antibiofilm Activity against Staphylococcus aureus

Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 115 ◽  
Author(s):  
Busi Siddhardha ◽  
Uday Pandey ◽  
K. Kaviyarasu ◽  
Rajasekharreddy Pala ◽  
Asad Syed ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Therapeutic Potential ◽  
Chitosan Nanoparticles ◽  
Cell Surface Hydrophobicity ◽  
Surface Hydrophobicity ◽  
Inhibitory Effect ◽  
Biological Properties ◽  
Antibiofilm Activity ◽  
Growth Curve Analysis ◽  
Biofilm Development

The application of nanotechnology in medicine is gaining popularity due to its ability to increase the bioavailability and biosorption of numerous drugs. Chrysin, a flavone constituent of Orocylumineicum vent is well-reported for its biological properties. However, its therapeutic potential has not been fully exploited due to its poor solubility and bioavailability. In the present study, chrysin was encapsulated into chitosan nanoparticles using TPP as a linker. The nanoparticles were characterized and investigated for their anti-biofilm activity against Staphylococcus aureus. At sub-Minimum Inhibitory Concentration, the nanoparticles exhibited enhanced anti-biofilm efficacy against S. aureus as compared to its bulk counterparts, chrysin and chitosan. The decrease in the cell surface hydrophobicity and exopolysaccharide production indicated the inhibitory effect of the nanoparticles on the initial stages of biofilm development. The growth curve analysis revealed that at a sub-MIC, the nanoparticles did not exert a bactericidal effect against S. aureus. The findings indicated the anti-biofilm activity of the chrysin-loaded chitosan nanoparticles and their potential application in combating infections associated with S. aureus.

scholarly journals Synthesis,1H NMR Structure, and Activity of a Three-disulfide-bridged Maurotoxin Analog Designed to Restore the Consensus Motif of Scorpion Toxins

2000 ◽  
Vol 275 (18) ◽  
pp. 13605-13612 ◽  
Author(s):  
Ziad Fajloun ◽  
Gilles Ferrat ◽  
Edmond Carlier ◽  
Mohamed Fathallah ◽  
Catherine Lecomte ◽  
...  
Keyword(s):  
1H Nmr ◽  
Nmr Structure ◽  
Scorpion Toxins ◽  
Consensus Motif ◽  
Structure And Activity

scholarly journals PIPER CHABA EXTRACTS WITH ANTIBIOFILM ACTIVITY INFLUENCE ANTIHYPERGLYCEMIC AND ANTIHYPERLIPIDEMIC RESPONSES IN DIABETIC WISTER RATS

2021 ◽  
pp. 44-49
Author(s):  
SULTANA RAJIA ◽  
KHADIZA KHANAM ◽  
UMME FARHANA ◽  
SOHANUR RAHMAN ◽  
RASHIDUL HAQUE
Keyword(s):  
Ethyl Acetate ◽  
Therapeutic Potential ◽  
Low Density Lipoprotein ◽  
Fasting Blood Glucose ◽  
Intraperitoneal Administration ◽  
Density Lipoprotein ◽  
Antimicrobial Activities ◽  
Positive Control ◽  
Diabetic Rats ◽  
Antibiofilm Activity

Objectives: Piper chaba, native to South and Southeast Asia, has been traditionally used as a medicinal plant. Aim of this study was to evaluate the antihyperglycemic and antihyperlipidemic activities of P. chaba root extracts (RE) in streptozotocin (STZ)-induced diabetic rats along with its antimicrobial activity. Methods: Diabetes was induced in Wister rats through the intraperitoneal administration of STZ (50 mg/kg b.w.). Antidiabetic and antilipidemic activities of the RE (in methanol, ethanol, ethyl acetate and distilled water) were evaluated by administering oral dose (200 mg/kg b.w.) for 21 days. Metformin (12.1 mg/kg b.w.) was used as a positive control. Blood samples of rats were drawn by tail vein puncture and cardiac puncture to determine the fasting blood glucose (FBG) and serum level of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), respectively. Standard protocols were followed to determine the antimicrobial and antibiofilm activities against two different strains of bacteria. Results: Oral administration of P. chaba RE for 21 days resulted in a significant (p< 0.001) decrease in FBG and TC, TG, and LDL levels (p<0.001), when compared to the untreated diabetic rats. Significant (p<0.001) increase of HDL was observed when ethyl acetate and aqueous RE were administered. Out of four, two extracts showed varying antimicrobial activities, particularly against the gram-positive bacteria.  Conclusion: It became evident for the first time that P. chaba extracts possess antimicrobial activities and can serve as biochemical compounds with great alternative therapeutic potential in the management of diabetes and hypercholesterolemia.

Linking sequence patterns and functionality of alpha-helical antimicrobial peptides

2018 ◽  
Vol 35 (16) ◽  
pp. 2713-2717 ◽  
Author(s):  
Igor E Eliseev ◽  
Ivan N Terterov ◽  
Anna N Yudenko ◽  
Olga V Shamova
Keyword(s):  
Antimicrobial Peptides ◽  
Rational Design ◽  
Therapeutic Potential ◽  
Deep Understanding ◽  
Supplementary Information ◽  
Helical Conformation ◽  
Efficient Design ◽  
Sequence Patterns ◽  
Functional Features ◽  
Natural Peptides

Abstract Motivation The rational design of antimicrobial peptides (AMPs) with increased therapeutic potential requires deep understanding of the determinants of their activities. Inspired by the computational linguistic approach, we hypothesized that sequence patterns may encode the functional features of AMPs. Results We found that α-helical and β-sheet peptides have non-intersecting pattern sets and therefore constructed new sequence templates using only helical patterns. Designed peptides adopted an α-helical conformation upon binding to lipids, confirming that the method captures structural and biophysical properties. In the antimicrobial assay, 5 of 7 designed peptides exhibited activity against Gram(+) and Gram(–) bacteria, with most potent candidate comparable to best natural peptides. We thus conclude that sequence patterns comprise the structural and functional features of α-helical AMPs and guide their efficient design. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Antimicrobial and Antibiofilm Activity of a Recombinant Fragment of β-Thymosin of Sea Urchin Paracentrotus lividus

Marine Drugs ◽  
2018 ◽  
Vol 16 (10) ◽  
pp. 366 ◽  
Author(s):  
Angelo Spinello ◽  
Maria Cusimano ◽  
Domenico Schillaci ◽  
Luigi Inguglia ◽  
Giampaolo Barone ◽  
...  
Keyword(s):  
Sea Urchin ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Paracentrotus Lividus ◽  
Md Simulations ◽  
Experimental Investigations ◽  
Antibiofilm Activity ◽  
Peptide Fragment ◽  
Recombinant Fragment ◽  
Bacterial Membranes

With the aim to obtain new antimicrobials against important pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa, we focused on antimicrobial peptides (AMPs) from Echinoderms. An example of such peptides is Paracentrin 1 (SP1), a chemically synthesised peptide fragment of a sea urchin thymosin. In the present paper, we report on the biological activity of a Paracentrin 1 derivative obtained by recombination. The recombinant paracentrin RP1, in comparison to the synthetic SP1, is 22 amino acids longer and it was considerably more active against the planktonic forms of S. aureus ATCC 25923 and P. aeruginosa ATCC 15442 at concentrations of 50 µg/mL. Moreover, it was able to inhibit biofilm formation of staphylococcal and P. aeruginosa strains at concentrations equal to 5.0 and 10.7 µg/mL, respectively. Molecular dynamics (MD) simulations allowed to rationalise the results of the experimental investigations, providing atomistic insights on the binding of RP1 toward models of mammalian and bacterial cell membranes. Overall, the results obtained point out that RP1 shows a remarkable preference for bacterial membranes, in excellent agreement with the antibacterial activity, highlighting the promising potential of using the tested peptide as a template for the development of novel antimicrobial agents.

scholarly journals The Host Defense Peptide LL-37 Selectively Permeabilizes Apoptotic Leukocytes

2008 ◽  
Vol 53 (3) ◽  
pp. 1027-1038 ◽  
Author(s):  
Åse Björstad ◽  
Galia Askarieh ◽  
Kelly L. Brown ◽  
Karin Christenson ◽  
Huamei Forsman ◽  
...  
Keyword(s):  
Host Defense ◽  
Acute Inflammation ◽  
Specific Activity ◽  
Apoptotic Cell ◽  
Density Lipoprotein ◽  
Eukaryotic Cells ◽  
Apoptotic Cells ◽  
Membrane Composition ◽  
Bacterial Membranes ◽  
Host Defense Peptide

ABSTRACT LL-37 is a cationic host defense peptide that is highly expressed during acute inflammation and that kills bacteria by poorly defined mechanisms, resulting in permeabilization of microbial membranes. High concentrations of LL-37 have also been reported to have cytotoxic effects against eukaryotic cells, but the peptide is clearly capable of differentiating between membranes with different compositions (eukaryotic versus bacterial membranes). Eukaryotic cells such as leukocytes change their membrane composition during apoptotic cell death, when they are turned into nonfunctional but structurally intact entities. We tested whether LL-37 exerted specific activity on apoptotic cells and found that the peptide selectively permeabilized the membranes of apoptotic human leukocytes, leaving viable cells unaffected. This activity was seemingly analogous to the direct microbicidal effect of LL-37, in that it was rapid, independent of known surface receptors and/or active cell signaling, and inhibitable by serum components such as high-density lipoprotein. A similar selective permeabilization of apoptotic cells was recorded for both NK cells and neutrophils. In the latter cell type, LL-37 permeabilized both the plasma and granule membranes, resulting in the release of both lactate dehydrogenase and myeloperoxidase. Apoptosis is a way for inflammatory cells to die silently and minimize collateral tissue damage by retaining tissue-damaging and proinflammatory substances within intact membranes. Permeabilization of apoptotic leukocytes by LL-37, accompanied by the leakage of cytoplasmic as well as intragranular molecules, may thus shift the balance between pro- and anti-inflammatory signals and in this way be of importance for the termination of acute inflammation.

scholarly journals Capsid Protein C of Tick-Borne Encephalitis Virus Tolerates Large Internal Deletions and Is a Favorable Target for Attenuation of Virulence

2002 ◽  
Vol 76 (7) ◽  
pp. 3534-3543 ◽  
Author(s):  
Regina M. Kofler ◽  
Franz X. Heinz ◽  
Christian W. Mandl
Keyword(s):  
Amino Acid ◽  
Capsid Protein ◽  
Protein C ◽  
Alpha Helix ◽  
Helical Conformation ◽  
Amino Acid Residues ◽  
Structural Class ◽  
Hydrophobic Domain ◽  
Tick Borne Encephalitis ◽  
Subviral Particles

ABSTRACT Deletions ranging in size from 4 to 21 amino acid residues were introduced into the capsid protein of the flavivirus tick-borne encephalitis (TBE) virus. These deletions incrementally affected a hydrophobic domain which is present at the center of all flavivirus capsid protein sequences and part of which may form an amphipathic alpha-helix. In the context of the full-length TBE genome, the deletions did not measurably affect protein expression and up to a deletion length of 16 amino acid residues, corresponding to almost 17% of mature protein C, viable virus was recovered. This virus was strongly attenuated but highly immunogenic in adult mice, revealing capsid protein C as a new and attractive target for the directed attenuation of flaviviruses. Apparently, the larger deletions interfered with the correct assembly of infectious virus particles, and this disturbance of virion assembly is likely to be the molecular basis of attenuation. However, all of the mutants carrying large deletions produced substantial amounts of subviral particles, which as judged from density gradient analyses were identical to recombinant subviral particles as obtained by the expression of the surface proteins prM and E alone. The structural and functional flexibility of protein C revealed in this study and its predicted largely alpha-helical conformation are reminiscent of capsid proteins of other enveloped viruses, such as alphaviruses (N-terminal domain of the capsid protein), retroviruses, and hepadnaviruses and suggest that all of these may belong to a common structural class, which is fundamentally distinct from the classical β-barrel structures of many icosahedral viral capsids. The possibility of attenuating flaviviruses by disturbing virus assembly and favoring the production of noninfectious but highly immunogenic subviral particles opens up a promising new avenue for the development of live flavivirus vaccines.

Sign in / Sign up

Export Citation Format

Share Document