Improving the Selectivity of Antimicrobial Peptides from Anuran Skin

Abstract

Anuran skin is known to be a rich source of antimicrobial peptides although their therapeutic potential is often limited due to their toxicity against mammalian cells. The analysis of structure-activity relationships among anuran antimicrobial peptides provided the parameters to construct the "Mutator" tool for improving their selectivity for bacterial cells, by suggesting appropriate point substitutions. Double substitution analogues [K2, K16] of the Xenopus tropicalis peptide XT-7 and [I2, K19] of the Ascaphus truei peptide ascaphin-8 were predicted by this tool to have an increased 'therapeutic index' (TI = HC(50)/MIC for erythrocytes with respect to bacteria) > 80. The mutated peptides were synthesized and respectively found to have experimental TI values > 130 for S. aureus or E. coli, a considerable improvement with respect to TI < 37 for the parent compounds. Circular dichroism studies of the mutated peptides suggested this may in part be due to variations in the α-helical structure. For P. aeruginosa, which is more resistant to XT-7, the TI increased in the mutated peptide from 5 to >270, also due to a significant improvement in minimal inhibitory concentration. We have shown that the Mutator tool is capable of suggesting limited variations in natural anuran peptides capable of increasing peptide selectivity, by decreasing toxicity against mammalian erythrocytes, in general without compromising antibacterial activity. The tool is freely available on the Mutator Web server at http://split4.pmfst.hr/mutator/.

Phenol‐Soluble‐Modulin‐Inspired Amphipathic Peptides Have Bactericidal Activity against Multidrug‐Resistant Bacteria

“…They have different emphases, but most of them can predict some aspects of a newly designed peptide drug according to their own algorithms. We mutated single or double amino acids of zp3 following the advice given by Mutator , an online computational tool, expecting to improve its antimicrobial activity . Peptides zp34 – zp36 were designed with the help of this application.…”

“…We mutated single or double amino acids of zp3 following the advice given by Mutator,a no nline computational tool, expecting to improve its antimicrobial activity. [27] Peptides zp34-zp36 were designed with the help of this application. Peptide-based moleculesf ace the difficult problemo fh igh sensitivity to proteolytic enzymes, which significantly hindert he in vivo medicinal efficacy.U nnatural d-form amino acid substitutions and cyclization are two simple yet efficient approaches to stabilizep eptides.…”

The Spectrum of Design Solutions for Improving the Activity-Selectivity Product of Peptide Antibiotics against Multidrug-Resistant Bacteria and Prostate Cancer PC-3 Cells

“…Mutator tool [25] server: http://mutator.djpept.com/ or http://splitbioinf.pmfst.hr/mutator/. Therapeutic Index Estimator [26] server: http://splitbioinf.pmfst.hr/split/dserv1/.…”

Analisis In Silico Aktivitas antimikroba Peptida dari Susu Kuda Sumbawa

“…Semakin tinggi nilai yang diperoleh semakin tinggi aktivitas antimikrobanya. Peptida LANSTEFAK yang merupakan hasil modifikasi peptida LVNELTEFAK yang sebelumnya diprediksi meningkatkan index terapi dan aktivitas antimikrobanya, pada analisis ini LANSTEFAK diprediksi meningkat aktivitasnya dibandingkan dengan LVNELTEFAK meskipun belum dapat dimasukkan dalam kategori peptida antimikroba (Kamech et al 2012;Kusumaningtyas et al 2016 Analisis selanjutnya menggunakan CAMP R3 (Collection of anti-microbial peptides) dibuat untuk mengembangkan dan mempercepat penelitian mengenai kelompok peptida antimikroba. Peptida antimikroba mempunyai kelompok-kelompok yang masing-masing mempunyai persamaan komposisi sekuen spesifik yang dapat mengarahkan penemuan peptida antimikroba yang baru.…”