Use of Peptide Libraries for Identification and Optimization of Novel Antimicrobial Peptides

Ashby, Martin; Petkova, Asya; Gani, Jurnorain; Mikut, Ralf; Hilpert, Kai

doi:10.2174/1568026616666160713125555

Cited by 41 publications

(22 citation statements)

References 100 publications

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“…Combinatorial libraries, prepared through chemical synthesis, or biological libraries such as phage display, represent powerful tools to optimize existing antimicrobial peptides [ 28 ]. By designing and screening a positional scanning library of Cap18, we successfully designed Cap18 peptide derivatives with changed species specificity and the potential to be used in target-specific antimicrobial therapy by introducing single amino acid substitutions in the original Cap18 sequence.…”

Section: Discussionmentioning

confidence: 99%

Dissection of the antimicrobial and hemolytic activity of Cap18: Generation of Cap18 derivatives with enhanced specificity

et al. 2018

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Due to the rapid emergence of resistance to classical antibiotics, novel antimicrobial compounds are needed. It is desirable to selectively kill pathogenic bacteria without targeting other beneficial bacteria in order to prevent the negative clinical consequences caused by many broad-spectrum antibiotics as well as reducing the development of antibiotic resistance. Antimicrobial peptides (AMPs) represent an alternative to classical antibiotics and it has been previously demonstrated that Cap18 has high antimicrobial activity against a broad range of bacterial species. In this study we report the design of a positional scanning library consisting of 696 Cap18 derivatives and the subsequent screening for antimicrobial activity against Y. ruckeri, A. salmonicida, S. Typhimurium and L. lactis as well as for hemolytic activity measuring the hemoglobin release of horse erythrocytes. We show that the hydrophobic face of Cap18, in particular I13, L17 and I24, is essential for its antimicrobial activity against S. Typhimurium, Y. ruckeri, A. salmonicida, E. coli, P. aeruginosa, L. lactis, L. monocytogenes and E. faecalis. In particular, Cap18 derivatives harboring a I13D, L17D, L17P, I24D or I24N substitution lost their antimicrobial activity against any of the tested bacterial strains. In addition, we were able to generate species-specific Cap18 derivatives by particular amino acid substitutions either in the hydrophobic face at positions L6, L17, I20, and I27, or in the hydrophilic face at positions K16 and K18. Finally, our data showed the proline residue at position 29 to be essential for the inherent low hemolytic activity of Cap18 and that substitution of the residues K16, K23, or G21 by any hydrophobic residues enhances the hemolytic activity. This study demonstrates the potential of generating species-specific AMPs for the selective elimination of bacterial pathogens.

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Section: Discussionmentioning

confidence: 99%

Dissection of the antimicrobial and hemolytic activity of Cap18: Generation of Cap18 derivatives with enhanced specificity

et al. 2018

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“…Using known aptamers or novel sequences identified by in-vitro selection in combination with subsequently selected competing immunogenic peptides, e.g. selected by powerful peptide library screening (which has been shown to be successfully applied for tumor-targeting 30 or antimicrobial peptides 31 ), would not only identify more such cross-recognitions but also result in a high affinity of the aptamer towards both targets, fostering practical applications. Almost any small molecule target may thus be addressed by an LF-assay applying the presented approach (without optimizing conditions in the very case presented) offering, however, a transferable concept for LAF assays for small molecules.…”

Section: Discussionmentioning

confidence: 99%

Small molecule detection with aptamer based lateral flow assays: Applying aptamer-C-reactive protein cross-recognition for ampicillin detection

Kaiser

Weisser

Kohl

et al. 2018

Sci Rep

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Aptamer-based lateral flow assays (LFAs) are an emerging field of aptamer applications due to numerous potential applications. When compared to antibodies, potential advantages like cost effectiveness or lower batch to batch variations are evident. The development of LFAs for small molecules, however, is still challenging due to several reasons, primarily linked to target size and accessible interaction sites. In small molecule analysis, however, aptamers in many cases are preferable since immunogenicity is not required and they may exhibit even higher target selectivity. We report the first cross-recognition of a small molecule (ampicillin) and a protein (C-reactive protein), predicted by in-silico analysis, then experimentally confirmed - using two different aptamers. These features can be exploited for developing an aptamer-based LFA for label-free ampicillin detection, functioning also for analysis in milk extract. Most importantly, the principal setup denotes a novel, transferable and versatile general approach for detection of small molecules using competitive LFAs, unlikely to be generally realized by aptamer-DNA-binding otherwise.

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“…With the technical advances on combinatorial chemistry and molecular biology, random peptide libraries with high capacity have become available [30,31]. The screening of these chemical or biological libraries is termed as biopanning.…”

Section: Biopanningmentioning

confidence: 99%

Molecular Design of Peptide-Fc Fusion Drugs

Lin

Zhou

et al. 2019

CDM

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Peptide-Fc fusion drugs are a category of biological therapeutics in which the Fc region of an antibody is genetically fused to a peptide of interest. In this review, we summarize the key steps in peptide-Fc fusion technology and stress the main computational resources, tools, and methods that have been used in the rational design of peptide-Fc fusion drugs. Additionally, open questions about the computer-aided molecular design of peptide-Fc are raised. Answers to these questions by future research will certainly help make the transition from peptide leads to drugs on the market quicker and cheaper.

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Use of Peptide Libraries for Identification and Optimization of Novel Antimicrobial Peptides

Cited by 41 publications

References 100 publications

Dissection of the antimicrobial and hemolytic activity of Cap18: Generation of Cap18 derivatives with enhanced specificity

Dissection of the antimicrobial and hemolytic activity of Cap18: Generation of Cap18 derivatives with enhanced specificity

Small molecule detection with aptamer based lateral flow assays: Applying aptamer-C-reactive protein cross-recognition for ampicillin detection

Molecular Design of Peptide-Fc Fusion Drugs

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