Synthetic peptides derived from human antimicrobial peptide ubiquicidin accumulate at sites of infections and eradicate (multi-drug resistant) Staphylococcus aureus in mice

Brouwer, Carlo P.J.M.; Bogaards, Sylvia J. P.; Wulferink, Marty; Velders, Markwin P.; Welling, Mick M.

doi:10.1016/j.peptides.2006.05.022

Cited by 53 publications

(61 citation statements)

References 17 publications

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“…The UBI29-41 peptide fragment proved to be more difficult to synthesize than the UBI30-41 peptide, requiring multiple attempts to produce satisfactory yields of the desired peptide. This was unexpected as previously published reports do not mention difficulties in the synthesis of UBI29-41 [5,6,22]. Since the syntheses were initiated at the Cterminus, it could be suggested that the problem may have occurred on addition of the last amino acid, threonine.…”

Section: Discussionmentioning

confidence: 85%

“…Peptides with sequences that give rise to beta sheet secondary structures, and those with very hydrophobic regions are most prone to aggregation and are generally the most problematic to synthesize [23,[28][29][30][31][32]. Sequence analysis of UBI29-41, using the Garnier-Robson and Chou-Fasman algorithms, predicted an alpha helical secondary structure for this peptide rather than a beta sheet structure [6,33,34].…”

Section: Discussionmentioning

confidence: 99%

“…Their biological role may also mean that they exhibit high selectivity for certain biological cell types or processes which may be of interest in the diagnosis of diseased individuals [4]. Such a biomolecule is ubiquicidin (UBI), a 6.6 kDa linear peptide (of 59 amino acids) that is found in humans and other eukaryotes [5,6]. This peptide exhibits broad spectrum antimicrobial activity against pathogenic bacteria and Candida spp.…”

Section: Introductionmentioning

confidence: 99%

“…Computer models suggest that this peptide contains alpha helices and beta sheets which allow it to bind to, and compromise the integrity of, prokaryote cell walls. Due to the difficulties in synthesizing the full-length peptide, studies were carried out with fragments of the peptide that are believed to be important in the preferential binding of the peptide to bacterial cells [6]. It was reported that certain fragments of UBI, including the 29-41 fragment exhibit features that make them good candidates for targeting vectors in the development of tracers for PET [5,7].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Peptide synthesis, characterization and 68Ga-radiolabeling of NOTA-conjugated ubiquicidin fragments for prospective infection imaging with PET/CT

Ebenhan

Chadwick

Sathekge

et al. 2014

Nuclear Medicine and Biology

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Peptide synthesis, characterization and 68Ga-radiolabeling of NOTA-conjugated ubiquicidin fragments for prospective infection imaging with PET/CT

Ebenhan

Chadwick

Sathekge

et al. 2014

Nuclear Medicine and Biology

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“…Of particular interest is the fragment UBI 31−38 ( Figure 1), which is relatively small, easily synthesized, and exhibits antibacterial activity toward methicillin resistant Staphylococcus aureus. 4 Peptides open up new perspectives in drug design by providing an entire range of highly selective and nontoxic pharmaceuticals. With growing applications of their synthesis and bioactivity, considerable attention has been focused on the research of peptide-based derivatives.…”

mentioning

confidence: 99%

Synthesis of a New Peptide–Coumarin Conjugate: A Potential Agent against Cryptococcosis

Ferreira

Carneiro

Lara

et al. 2015

ACS Med. Chem. Lett.

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Antimicrobial peptides (AMPs) are currently being investigated as potential sources of novel therapeutics against an increasing number of microorganisms resistant to conventional antibiotics. The conjugation of an AMP to other bioactive compounds is an interesting approach for the development of new derivatives with increased antimicrobial efficiency and broader spectra of action. In this work, the synthesis of a new peptide−coumarin conjugate via copper(I)-catalyzed azide−alkyne cycloaddition is described. The conjugate was assayed for in vitro cytotoxicity and displayed antifungal activity against Cryptococcus gattii and Cryptococcus neoformans. Additionally, the conjugate exhibited increased antifungal efficacy when compared with the individual peptide, coumarin, or triazole moieties. Treatment of C. gattii with the peptide−coumarin conjugate enhanced the production of reactive oxygen species, suggesting that the oxidative burst plays an important role in the mechanism of action of the conjugate. KEYWORDS: Antimicrobial peptide, copper(I)-catalyzed azide−alkyne cycloaddition, coumarin, cryptococcosis, reactive oxygen species A ntimicrobial peptides (AMPs) are small molecular weight proteins with antimicrobial activity against bacteria, viruses, and fungi. 1 AMPs are currently being investigated as potential sources of novel therapeutic antimicrobial agents because of their broad-spectrum activity and low susceptibility for developing resistance. 2 Ubiquicidin (UBI) is an antimicrobial peptide, which was first isolated from murine macrophages and then found at low concentrations (as a first line of defense) inside human airway epithelial cells, activated macrophages, and in human colon mucosa. UBI is a cationic peptide consisting of 59 amino acid residues. It is not expected to be immunogenic to humans since it is of human origin. 3 UBI 1−59 and some of its fragments have been shown to be microbicidal against a broad spectrum of pathogens. Of particular interest is the fragment UBI 31−38 (Figure 1), which is relatively small, easily synthesized, and exhibits antibacterial activity toward methicillin resistant Staphylococcus aureus. 4 Peptides open up new perspectives in drug design by providing an entire range of highly selective and nontoxic pharmaceuticals. With growing applications of their synthesis and bioactivity, considerable attention has been focused on the research of peptide-based derivatives. 5 Coumarins form an important class of benzopyrones, which are found in nature. Many coumarins and their derivatives possess antimicrobial, anti-inflammatory, and anticancer properties. 6 Research on coumarin compounds as antifungal agents has shown that structural modification of the coumarin skeleton (i.e., the benzene ring, lactone ring, or both) results in derivatives, which possess potent antifungal activity when compared to clinically used antifungal drugs. 7 Therefore, numerous efforts have focused on the development of coumarins as potential drugs. 8 The copper(I)-catalyzed azide−alkyne cyclo...

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Synthetic Mimics of Antimicrobial Peptides—A Versatile Ring‐Opening Metathesis Polymerization Based Platform for the Synthesis of Selective Antibacterial and Cell‐Penetrating Polymers

Lienkamp

Tew

2009

Chemistry A European J

145

139

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Natural macromolecules exhibit an extensive arsenal of properties, many of which have proven difficult to recapitulate in simpler synthetic systems. Over the last couple of years, foldamers have emerged as one important step toward increased functionality in synthetic systems. While the great majority of work in this area has focused on folded structures, hence the name, more recent progress has centered on polymers that mimic protein function. These efforts have resulted in the design of relatively simple macromolecules; one example are the synthetic mimics of antimicrobial peptides (SMAMPs) that capture the central physicochemical features of their natural archetypes irrespective of the specific folded form. Here we present our recent efforts to create polymers which display biological activity similar to natural proteins, including antimicrobial and cell-penetrating peptides.

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Synthetic peptides derived from human antimicrobial peptide ubiquicidin accumulate at sites of infections and eradicate (multi-drug resistant) Staphylococcus aureus in mice

Cited by 53 publications

References 17 publications

Peptide synthesis, characterization and 68Ga-radiolabeling of NOTA-conjugated ubiquicidin fragments for prospective infection imaging with PET/CT

Peptide synthesis, characterization and 68Ga-radiolabeling of NOTA-conjugated ubiquicidin fragments for prospective infection imaging with PET/CT

Synthesis of a New Peptide–Coumarin Conjugate: A Potential Agent against Cryptococcosis

Synthetic Mimics of Antimicrobial Peptides—A Versatile Ring‐Opening Metathesis Polymerization Based Platform for the Synthesis of Selective Antibacterial and Cell‐Penetrating Polymers

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