scholarly journals Effects of Dimerization on the Structure and Biological Activity of Antimicrobial Peptide Ctx-Ha

2012 ◽  
Vol 56 (6) ◽  
pp. 3004-3010 ◽  
Author(s):  
E. N. Lorenzón ◽  
G. F. Cespedes ◽  
E. F. Vicente ◽  
L. G. Nogueira ◽  
T. M. Bauab ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Biological Activity ◽  
Antimicrobial Peptide ◽  
Hemolytic Activity ◽  
Pore Diameter ◽  
Solid Phase ◽  
Biological Activities ◽  
Solid Phase Peptide Synthesis ◽  
Activity Assay ◽  
Growth Of Bacteria

ABSTRACTIt is well known that cationic antimicrobial peptides (cAMPs) are potential microbicidal agents for the increasing problem of antimicrobial resistance. However, the physicochemical properties of each peptide need to be optimized for clinical use. To evaluate the effects of dimerization on the structure and biological activity of the antimicrobial peptide Ctx-Ha, we have synthesized the monomeric and three dimeric (Lys-branched) forms of the Ctx-Ha peptide by solid-phase peptide synthesis using a combination of 9-fluorenylmethyloxycarbonyl (Fmoc) andt-butoxycarbonyl (Boc) chemical approaches. The antimicrobial activity assay showed that dimerization decreases the ability of the peptide to inhibit growth of bacteria or fungi; however, the dimeric analogs displayed a higher level of bactericidal activity. In addition, a dramatic increase (50 times) in hemolytic activity was achieved with these analogs. Permeabilization studies showed that the rate of carboxyfluorescein release was higher for the dimeric peptides than for the monomeric peptide, especially in vesicles that contained sphingomyelin. Despite different biological activities, the secondary structure and pore diameter were not significantly altered by dimerization. In contrast to the case for other dimeric cAMPs, we have shown that dimerization selectively decreases the antimicrobial activity of this peptide and increases the hemolytic activity. The results also show that the interaction between dimeric peptides and the cell wall could be responsible for the decrease of the antimicrobial activity of these peptides.

scholarly journals Novel Cyclic Lipopeptide Antibiotics: Effects of Acyl Chain Length and Position

2020 ◽  
Vol 21 (16) ◽  
pp. 5829 ◽  
Author(s):  
Signe Kaustrup Jensen ◽  
Thomas T. Thomsen ◽  
Alberto Oddo ◽  
Henrik Franzyk ◽  
Anders Løbner-Olesen ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Fatty Acid ◽  
Chain Length ◽  
Peptide Synthesis ◽  
Hemolytic Activity ◽  
Cyclic Peptide ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Resistant Bacteria ◽  
Cyclic Lipopeptide

Multidrug-resistant bacteria are a global health problem. One of the last-resort antibiotics against Gram-negative bacteria is the cyclic lipopeptide colistin, displaying a flexible linker with a fatty acid moiety. The aim of the present project was to investigate the effect on antimicrobial activity of introducing fatty acid moieties of different lengths and in different positions in a cyclic peptide, S3(B), containing a flexible linker. The lipidated analogues of S3(B) were synthesized by 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis. Following assembly of the linear peptide by Fmoc solid-phase peptide synthesis, on-resin head-to-tail cyclization and fatty acid acylation were performed. The antimicrobial activity was determined against the ESKAPE pathogens, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli. Furthermore, hemolytic activity was determined against human erythrocytes. A total of 18 cyclic lipopeptides were synthesized and characterized. It was found that introduction of fatty acids in positions next to the flexible linker was more strongly linked to antimicrobial activity. The fatty acid length altered the overall hydrophobicity, which was the driving force for both high antimicrobial and hemolytic activity. Peptides became highly hemolytic when carbon-chain length exceeded 10 (i.e., C10), overlapping with the optimum for antimicrobial activity (i.e., C8–C12). The most promising candidate (C8)5 showed antimicrobial activity corresponding to that of S3(B), but with an improved hemolytic profile. Finally, (C8)5 was further investigated in a time-kill experiment.

Solid-phase peptide synthesis and biological activity of bovine thymopoietin II (bTP-11)

2009 ◽  
Vol 44 (2) ◽  
pp. 183-191 ◽  
Author(s):  
D. DAVID SMITH ◽  
J. MICHAEL CONLON ◽  
JANIS PETZEL ◽  
LEI CHEN ◽  
RICHARD F. MURPHY ◽  
...  
Keyword(s):  
Biological Activity ◽  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis

scholarly journals Betalains in Edible Fruits of Three Cactaceae Taxa—Epiphyllum, Hylocereus, and Opuntia—Their LC-MS/MS and FTIR Identification and Biological Activities Evaluation

Plants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 2669
Author(s):  
Michaela Barkociová ◽  
Jaroslav Tóth ◽  
Katarzyna Sutor ◽  
Natalia Drobnicka ◽  
Slawomir Wybraniec ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antioxidant Activity ◽  
Food Industry ◽  
Biological Activities ◽  
Ornamental Plants ◽  
Reducing Power ◽  
Activity Assay ◽  
Natural Pigment ◽  
E Coli ◽  
Ft Ir

Epiphyllum, Hylocereus, and Opuntia plants belong to the Cactaceae family. They are mostly known as ornamental plants but also for their edible fruits, which can potentially be sources of betalains, such as betanin, a natural pigment used in the food industry, e.g., under the European label code E 162. The aim of this work was the identification of betalains (using LC-MS/MS), evaluation of total betalain content (spectrophotometrically), analysis of functional groups (using FT-IR), evaluation of antioxidant activity (using DPPH, ABTS, FRAP, DCFH-DA, and reducing power methods) and evaluation of antimicrobial activity (S. aureus, E. coli, and C. albicans) in fruits of Epiphyllum, Hylocereus, and Opuntia taxa. A total of 20 betalains were identified in the studied Cactaceae fruits. The Epiphyllum pink hybrid had the highest values of total betalains amongst all samples. The highest antioxidant activity was observed in the Epiphyllum pink hybrid, in Opuntia zacuapanensis and O. humifusa fruits. The antimicrobial activity assay showed that cacti fruits were not able to effectively inhibit the growth of E. coli, S. aureus, or C. albicans. Our results prove that these fruits are good sources of natural pigments—betalains. They do not contain toxic compounds in significant amounts and they exhibit antioxidant activity.

Design, synthesis and biological activities of pyrrole-3-carboxamide derivatives as EZH2 (enhancer of zeste homologue 2) inhibitors and anticancer agents

2020 ◽  
Vol 44 (6) ◽  
pp. 2247-2255
Author(s):  
Qifan Zhou ◽  
Lina Jia ◽  
Fangyu Du ◽  
Xiaoyu Dong ◽  
Wanyu Sun ◽  
...  
Keyword(s):  
Biological Activity ◽  
Anticancer Agents ◽  
Biological Activities ◽  
Activity Assay ◽  
Design Synthesis ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Enhancer Of Zeste

A novel series of pyrrole-3-carboxamides targeting EZH2 have been designed and synthesized. The structure–activity relationships were summarized by combining with in vitro biological activity assay and docking results.

Structure-guided de novo design of α-helical antimicrobial peptide with enhanced specificity

2010 ◽  
Vol 82 (1) ◽  
pp. 243-257 ◽  
Author(s):  
Jin-Feng Huang ◽  
Yi-Min Xu ◽  
Dian-Ming Hao ◽  
Yi-Bing Huang ◽  
Yu Liu ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Amino Acid ◽  
Hemolytic Activity ◽  
De Novo ◽  
Biological Activities ◽  
Peptide Sequence ◽  
Rational Approach ◽  
Peptide Antibiotics ◽  
Self Association ◽  
Lysine Substitution

In the present study, the 26-residue peptide sequence Ac-KWKSFLKTFKSAKKTVLHTALKAISS-amide (peptide P) was utilized as the framework to study the effects of introducing hydrophilic amino acid lysine on the nonpolar face of the helix on peptide biological activities. Lysine residue was systematically used to substitute original hydrophobic amino acid at the selected locations on the nonpolar face of peptide P. In order to compensate for the loss of hydrophobicity caused by lysine substitution, leucine was also used to replace original alanine to increase peptide overall hydrophobicity. Hemolytic activity is correlated with peptide hydrophobicity. By introducing lysine on the nonpolar face, we significantly weaken peptide hemolytic activity as well as antimicrobial activity. However, by utilizing leucine to compensate the hydrophobicity, we improve antimicrobial activity against both Gram-negative and -positive bacteria. Peptide self-association ability and hydrophobicity were also determined. This specific rational approach of peptide design could be a powerful method to optimize antimicrobial peptides with clinical potential as peptide antibiotics.

scholarly journals Evaluating the Bioactivity of a Novel Broad-Spectrum Antimicrobial Peptide Brevinin-1GHa from the Frog Skin Secretion of Hylarana guentheri and Its Analogues

Toxins ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 413 ◽  
Author(s):  
Qi Chen ◽  
Peng Cheng ◽  
Chengbang Ma ◽  
Xinping Xi ◽  
Lei Wang ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Peptide ◽  
Broad Spectrum ◽  
Hemolytic Activity ◽  
High Performance ◽  
Disulfide Bridge ◽  
Reversed Phase ◽  
Central Position ◽  
Skin Secretion ◽  
Mass Spectral

Many antimicrobial peptides (AMPs) have been identified from the skin secretion of the frog Hylarana guentheri (H.guentheri), including Temporin, Brevinin-1, and Brevinin-2. In this study, an antimicrobial peptide named Brevinin-1GHa was identified for the first time by using ‘shotgun’ cloning. The primary structure was also confirmed through mass spectral analysis of the skin secretion purified by reversed-phase high-performance liquid chromatography (RP-HPLC). There was a Rana-box (CKISKKC) in the C-terminal of Brevinin-1GHa, which formed an intra-disulfide bridge. To detect the significance of Rana-box and reduce the hemolytic activity, we chemically synthesized Brevinin-1GHb (without Rana-box) and Brevinin-1GHc (Rana-box in central position). Brevinin-1GHa exhibited a strong and broad-spectrum antimicrobial activity against seven microorganisms, while Brevinin-1GHb only inhibited the growth of Staphylococcus aureus (S. aureus), which indicates Rana-box was necessary for the antimicrobial activity of Brevinin-1GHa. The results of Brevinin-1GHc suggested transferring Rana-box to the central position could reduce the hemolytic activity, but the antimicrobial activity also declined. Additionally, Brevinin-1GHa demonstrated the capability of permeating cell membrane and eliminating biofilm of S. aureus, Escherichia coli (E. coli), and Candida albicans (C. albicans). The discovery of this research may provide some novel insights into natural antimicrobial drug design.

scholarly journals Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

2018 ◽  
Vol 14 ◽  
pp. 1112-1119 ◽  
Author(s):  
Dan Liu ◽  
Ya-Li Guo ◽  
Jin Qu ◽  
Chi Zhang
Keyword(s):  
Peptide Synthesis ◽  
Cyclic Peptide ◽  
Solid Phase ◽  
Biological Activities ◽  
Solid Phase Peptide Synthesis ◽  
Coupling Reaction ◽  
Hypervalent Iodine ◽  
Peptide Coupling ◽  
Cyclic Peptide Synthesis ◽  
Cyclic Heptapeptide

The system of the hypervalent iodine(III) reagent FPID and (4-MeOC6H4)3P was successfully applied to solid-phase peptide synthesis and cyclic peptide synthesis. Four peptides with biological activities were synthesized through SPPS and the bioactive cyclic heptapeptide pseudostellarin D was obtained via solution-phase peptide synthesis. It is worth noting that FPID can be readily regenerated after the peptide coupling reaction.

Synthesis, biological activity and receptor binding affinity of two [8-arginine]vasopressin analogues with inhibitory properties

1988 ◽  
Vol 53 (11) ◽  
pp. 2907-2913 ◽  
Author(s):  
Franciszek Kasprzykowski ◽  
Zbigniew Grzonka ◽  
Jiřina Slaninová ◽  
Tomislav Barth ◽  
Peter Crause ◽  
...  
Keyword(s):  
Biological Activity ◽  
Arginine Vasopressin ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Synthesis Method ◽  
The Other ◽  
Binding Affinities ◽  
Bovine Kidney ◽  
Liver Membranes ◽  
Vasopressin Analogues

Two analogues of arginine-vasopressin: [1-(β-mercapto-β,β-cyclopentamethylenepropionic acid), 2-D-phenylalanine, 7-sarcosine, 8-arginine]vasopressin and [1-(β-mercapto-β,β-cyclopentamethylenepropionic acid), 2-D-phenylalanine, 7-N-methylalanine, 8-arginine]vasopressin were synthesized by solid-phase peptide synthesis method. Both peptides exhibit antioxytocic, antivasopressor and antiglycogenolytic activities, and on the other hand they are weak antidiuretic agonists. The binding affinities of both analogues to oxytocic receptor (guinea pig myometrium membranes) and to hepatic V1 receptor (rat liver membranes) are practically the same as for the parent hormones, whereas the binding affinities to renal V2 receptor (bovine kidney membranes) are 60-90 times lower than for vasopressin.

Intein based bioprocess for production of a synthetic antimicrobial peptide: an alternative route to solid phase peptide synthesis

RSC Advances ◽  
2014 ◽  
Vol 4 (60) ◽  
pp. 31564-31572 ◽  
Author(s):  
Anindya Basu ◽  
Biswajit Mishra ◽  
Sharmistha Dey ◽  
Susanna Su Jan Leong
Keyword(s):  
Antimicrobial Peptide ◽  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Alternative Route ◽  
Synthesis Strategy ◽  
Peptide Candidate

Intein based bioprocessing strategy for producing antimicrobial peptide candidate was found to be more sustainable compared to solid phase peptide synthesis strategy (SPPS).

scholarly journals Towards the production of tikitericin: A novel peptide from Thermogemmatispora strain T81

2021 ◽  
Author(s):  
◽  
Benjamin Baker
Keyword(s):  
Antimicrobial Activity ◽  
Natural Products ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Genome Mining ◽  
New Drugs ◽  
Taupo Volcanic Zone ◽  
Ms Imaging ◽  
Modified Peptides ◽  
Microbial Natural Products

<p>The utilisation of natural products for treatment of human ailments has been rooted in various cultures for centuries. Extraction of natural products has been essential for the discovery of new drugs and inspiration for synthetic analogues. Since the success of penicillin, microbial natural products have been of interest. Genome mining of Thermogemmatisporastrain T81, a thermophile from the Taupo Volcanic Zone, found the potential for the production of novel ribosomally synthesised and post-translationally modified peptides (RiPPs). Previous work showed that T81 exhibited antimicrobial activity against a wide variety of extremophillic bacteria. Although the three thiopeptides encoded forin the genome of T81 have not been found, the lanthipeptide tikitericin has recently been isolated and described. Unfortunately tikitericin is produced in low quantities by T81 andbioactivity data has not yet been obtained. Because of its potential antimicrobial activity, different routes to produce it are of interest. The aim of this project wasto synthesisetikitericin by solid phase peptide synthesis. MS imaging was also utilised to search for the presence of tikitericin as an antimicrobial agent in situ.</p>

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