Development of novel antibacterial peptides that kill resistant isolates

Čudić, Mare; Condie, Barry A.; Weiner, Daniel J.; Лысенко, Елена; Xiang, Zhi Quan; Insug, O; Bulet, Philippe; Ötvös, László

doi:10.1016/s0196-9781(02)00244-9

Cited by 94 publications

(107 citation statements)

References 38 publications

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“…One feature that stands out among these peptides is the high amount of proline, which is known to dominate in some antibacterial peptides (Cudic et al, 2002). Specificity of isolated phage clones for S. typhimurium was demonstrated using two variations of ELISA (phage capture and Salmonella capture) and confirmed by precipitation assay, fiuorescence and electron microscopy.…”

Section: Discussionmentioning

confidence: 98%

Landscape phage probes for Salmonella typhimurium

Sorokulova

Olsen

Chen

et al. 2005

Journal of Microbiological Methods

109

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Section: Discussionmentioning

confidence: 98%

Landscape phage probes for Salmonella typhimurium

Sorokulova

Olsen

Chen

et al. 2005

Journal of Microbiological Methods

109

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“…[23][24][25]. Triplicate samples of native and cyclic peptides were assayed simultaneously at a concentration of 20 M. At 0, 4, 8, 12, 16, and 24 h, 200 l of the mixture was removed and added to 100 l of 15% aqueous trichloroacetic acid to precipitate serum proteins.…”

Section: Methodsmentioning

confidence: 99%

Engineering stable peptide toxins by means of backbone cyclization: Stabilization of the α-conotoxin MII

Clark

Fischer

Dempster

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

215

222

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Conotoxins (CTXs), with their exquisite specificity and potency, have recently created much excitement as drug leads. However, like most peptides, their beneficial activities may potentially be undermined by susceptibility to proteolysis in vivo. By cyclizing the ␣-CTX MII by using a range of linkers, we have engineered peptides that preserve their full activity but have greatly improved resistance to proteolytic degradation. The cyclic MII analogue containing a seven-residue linker joining the N and C termini was as active and selective as the native peptide for native and recombinant neuronal nicotinic acetylcholine receptor subtypes present in bovine chromaffin cells and expressed in Xenopus oocytes, respectively. Furthermore, its resistance to proteolysis against a specific protease and in human plasma was significantly improved. More generally, to our knowledge, this report is the first on the cyclization of disulfide-rich toxins. Cyclization strategies represent an approach for stabilizing bioactive peptides while keeping their full potencies and should boost applications of peptide-based drugs in human medicine.conotoxins ͉ drug delivery ͉ molecular engineering V enoms from marine snails of the Conus genus comprise a myriad of peptides called conotoxins (CTXs) for the rapid immobilization of prey (1, 2). These 12-to 30-aa peptides target membrane receptors with exquisite selectivity and potency and have become invaluable neurophysiological probes and drug leads. Recently, the CTX ziconotide (MVIIA) was approved for use in the treatment of severe chronic pain by the FDA, and other CTXs have entered clinical trials as treatments for pain (3,4). In addition, CTXs have played a critical role in dissecting the molecular mechanisms of ion channel and transporter functions in the nervous system (2). One family of CTXs, the ␣-CTXs, consists of members that antagonize the nicotinic acetylcholine receptors (nAChRs). Ranging in size from 12 to 19 residues, ␣-CTXs are the smallest of all of the CTXs, yet this family is the most widely distributed among Conus venoms (5).Despite their exciting applications, many peptide toxins are susceptible to enzymatic degradation by proteases. This characteristic may limit the therapeutic applications of CTXs, and, hence, methods that provide improvements in biological half-life are valuable. Cyclization has been used in the past as a strategy in the pharmaceutical industry for stabilizing and locking the conformation of small peptides (6). Similarly, microorganisms are known to produce cyclized peptides, such as cyclosporin A, which is now in widespread use as an immunosuppressant. Such a strategy has not been applied in the past to disulfide-rich proteins, but with the recent discovery of the cyclotide family of macrocyclic miniproteins (7), it is clear that the approach can be applied to disulfide-rich toxins to produce additional stabilization with the potential to dramatically increase the therapeutic potential of these molecules when limited by poor in vivo stability.This stu...

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“…2), a peptide their group originally isolated from the European sapsucking bug Pyrrhocoris apterus (Cociancich et al, 1994). In a couple of publications they report that pyrrhocloricin is non-toxic to eukaryotic cells and healthy mice, has good activity against model bacterial strains in vitro and when administered intravenously in vivo, and can protect mice from systemic E. coli challenge (Cudic et al, 2002;Cudic et al, 2003;Otvos et al, 2000a). Although pyrrhocoricin is toxic to infected animals at a high dose (50 mg/kg), its derivative in which the peptide is protected from exopeptidase cleavage by replacement of the N-terminal Val1 with 1-amino-cyclohexane-carboxylic acid and the C-terminal Asn20 with acetylated 2,3-diamino-propionic acid lacks this high dose toxicity and shows improved protease resistance, while maintaining the in vitro and in vivo efficacy over a broad concentration and dose range.…”

Section: Insectsmentioning

confidence: 99%