Antibiotic activity and structural analysis of the scorpion-derived antimicrobial peptide IsCT and its analogs

Lee, Kyungik; Shin, Song Yub; Kim, Kyoungho; Lim, Shin Saeng; Hahm, Kyung‐Soo; Kim, Yangmee

doi:10.1016/j.bbrc.2004.08.144

Cited by 77 publications

(65 citation statements)

References 28 publications

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“…Mutations of glycines to alanines at positions 13 and 17 increased both overall the helical content and hemolytic activity against erythrocytes [28]. Similar observations were made about the scorpion-derived AMP IsCT and its analogs, although there is no direct evidence of a carpet-based mechanism [27]. The major families of helical peptides which operate by the carpet mechanism include the dermaseptins [37] and cecropins [17].…”

Section: Discussionsupporting

confidence: 56%

Molecular dynamics investigation of the influence of anionic and zwitterionic interfaces on antimicrobial peptides’ structure: Implications for peptide toxicity and activity

Khandelia

Kaznessis

2006

Peptides

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Molecular dynamics simulations of three related helical antimicrobial peptides have been carried out in zwitterionic diphosphocholine (DPC) micelles and anionic sodiumdodecylsulfate (SDS) micelles. These systems can be considered as model mammalian and bacterial membrane interfaces, respectively. The goal of this study is to dissect the differences in peptide composition which make the mutant peptides (novispirin-G10 and novispirin-T7) less toxic than the parent peptide ovispirin (OVIS), although all three peptides have highly antibacterial properties. Compared to G10 and T7, OVIS inserts deepest into the DPC micelle. This correlates well with the lesser toxicity of G10 and T7. There is strong evidence which suggests that synergistic binding of hydrophobic residues drives binding of OVIS to the micelle. The helical content of G10 and T7 is reduced in the presence of DPC, and this leads to less amphipathic peptide structures, which bind weakly to the micelle. Simulations in SDS were carried out to compare the influence of membrane electrostatics on peptide structure. All three peptides bound strongly to SDS, and retained helical form. This corresponds well with their equally potent antibacterial properties. Based on the simulations, we argue that secondary structure stability often leads to toxic properties. We also propose that G10 and T7 operate by the carpet mechanism of cell lysis. Toxicity of peptides operating by the carpet mechanism can be attenuated by reducing the peptide helical content. The simulations successfully capture experimental binding states, and the different depths of binding of the three peptides to the two micelles correlate with their antibacterial and toxic properties.

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Section: Discussionsupporting

confidence: 56%

Molecular dynamics investigation of the influence of anionic and zwitterionic interfaces on antimicrobial peptides’ structure: Implications for peptide toxicity and activity

Khandelia

Kaznessis

2006

Peptides

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“…Several short-chain antimicrobial peptide toxins had been found in scorpions: DefLq (Leiurus quinquestriatu) (Cociancich et al 1993), androctonin, buthinin and Def1Aa (Androctonus australis) (Laurence et al 1996), Cll-dlp (Centruroides limpidus limpidus) (Rodríguez et al 2004), and IsCT (Opisthacanthus madagascariensis) (Leea et al 2004). Until now, BmK AS is the first long-chain scorpion neurotoxin that has antimicrobial activity.…”

Section: Discussionmentioning

confidence: 98%

Cloning, expression, and pharmacological activity of BmK AS, an active peptide from scorpion Buthus martensii Karsch

Shao

Wang

et al. 2007

Biotechnol Lett

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BmK AS is a beta long-chain scorpion peptide from the venom of Buthus martensii Karsch (BmK). It was efficiently expressed as a soluble and functional peptide in Escherichia coli, and purified by metal chelating chromatography. About 4.2 mg/l purified recombinant BmK AS could be obtained. The recombinant BmK AS maintained a similar analgesic activity to the natural one in both the mouse-twisting test and hot-plate procedure. It also exhibited antimicrobial activity against both Gram-positive and Gram-negative bacteria. BmK AS is the first long-chain scorpion peptide reported to have antimicrobial activity, and is a valuable molecular scaffold for pharmacological research.

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“…The balance between antimicrobial and hemolytic effects has been discussed in numerous works [116,[140][141][142][143][144][145][146][147][148][149][150][151]. The hemolytic effect is especially pronounced for Ltc 2a (Table 4).…”

Section: Hemolysismentioning

confidence: 99%

Latarcins: versatile spider venom peptides

Dubovskii

Vassilevski

Kozlov

et al. 2015

Cell. Mol. Life Sci.

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Arthropod venoms feature the presence of cytolytic peptides believed to act synergetically with neurotoxins to paralyze prey or deter aggressors. Many of them are linear, i.e., lack disulfide bonds. When isolated from the venom, or obtained by other means, these peptides exhibit common properties. They are cationic; being mostly disordered in aqueous solution, assume amphiphilic α-helical structure in contact with lipid membranes; and exhibit general cytotoxicity, including antifungal, antimicrobial, hemolytic, and anticancer activities. To suit the pharmacological needs, the activity spectrum of these peptides should be modified by rational engineering. As an example, we provide a detailed review on latarcins (Ltc), linear cytolytic peptides from Lachesana tarabaevi spider venom. Diverse experimental and computational techniques were used to investigate the spatial structure of Ltc in membrane-mimicking environments and their effects on model lipid bilayers. The antibacterial activity of Ltc was studied against a panel of Gram-negative and Gram-positive bacteria. In addition, the action of Ltc on erythrocytes and cancer cells was investigated in detail with confocal laser scanning microscopy. In the present review, we give a critical account of the progress in the research of Ltc. We explore the relationship between Ltc structure and their biological activity and derive molecular characteristics, which can be used for optimization of other linear peptides. Current applications of Ltc and prospective use of similar membrane-active peptides are outlined.

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Antibiotic activity and structural analysis of the scorpion-derived antimicrobial peptide IsCT and its analogs

Cited by 77 publications

References 28 publications

Molecular dynamics investigation of the influence of anionic and zwitterionic interfaces on antimicrobial peptides’ structure: Implications for peptide toxicity and activity

Molecular dynamics investigation of the influence of anionic and zwitterionic interfaces on antimicrobial peptides’ structure: Implications for peptide toxicity and activity

Cloning, expression, and pharmacological activity of BmK AS, an active peptide from scorpion Buthus martensii Karsch

Latarcins: versatile spider venom peptides

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