Effects of Cyclic Lipodepsipeptide Structural Modulation on Stability, Antibacterial Activity, and Human Cell Toxicity

Bionda, Nina; Stawikowski, Maciej; Stawikowska, Roma; Čudić, Mare; López‐Vallejo, Fabian; Treitl, Daniela; Medina-Franco, José L.; Čudić, Predrag

doi:10.1002/cmdc.201200016

Cited by 53 publications

(88 citation statements)

References 95 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, in 2006, approval was given for treatment of bacteraemia and right-sided endocarditis caused by MSSA and MRSA. 3 Although many cyclic lipopeptide antibiotics have been discovered, 4,5 daptomycin remains the only member of this class that is approved for clinical use.…”

Section: Antimicrobial Spectrum and Clinical Usementioning

confidence: 99%

“…The common peptide moiety contains 13 amino acids, six of which are non-proteinogenic: D-Asn (2) , ornithine (Orn (6) ), D-Ala (8) , D-Ser (11) , (2S,3R)-methylglutamate (MeGlu (12) ), and kynurenine (Kyn (13) ). The C-terminal ten amino acids form a macrocyclic core, which contains a ring-closing depsi (ester) bond between the side chain of Thr (4) and the α-COOH of the C-terminal Kyn (13) . 23,24 The N-terminal tripeptide protrudes from the ring and carries the variable fatty acyl residue, which is attached to Trp (1) .…”

Section: Structure and Biosynthesismentioning

confidence: 99%

“…The side chain and carbonyl group of Dab (9) of the other molecule interact with a water molecule that also binds to the peripheral Ca 2+ . The dimers are also connected by an interaction between the peripheral Ca 2+ and the carboxyl groups of mAsp (4) . There is a tunnel through the centre of the dimer, which is large enough to accommodate a phospholipid molecule.…”

Section: Structure Of Tsushimycinmentioning

confidence: 99%

“…49,52 Replacing Kyn (13) with Tyr, or (2S,3R)-MeGlu (12) with (2S,3S)-MeGlu or Thr (4) with Ser resulted in a 35 to 60-fold loss of activity at 5 mM Ca 2+ . Interestingly, at increased calcium concentrations, the activity of these peptides increased greatly and approached that of native daptomycin, which suggests that these modifications mainly affect Ca 2+ affinity but might have little effect on other aspects of daptomycin's action mechanism.…”

Section: Functional Effects Of Single or Combined Amino Acid Substitumentioning

confidence: 99%

“…Readers interested in learning more about these topics are referred to several previous reviews. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] …”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The action mechanism of daptomycin

Taylor

Palmer

2016

Bioorganic & Medicinal Chemistry

210

172

View full text Add to dashboard Cite

Daptomycin is a lipopeptide antibiotic produced by the soil bacterium Streptomyces roseosporus that is clinically used to treat severe infections with Grampositive bacteria. In this review, we discuss the mode of action of this important antibiotic. Although daptomycin is structurally related to amphomycin and similar lipopeptides that inhibit peptidoglycan biosynthesis, experimental studies have not produced clear evidence that daptomycin shares their action mechanism. Instead, the best characterized effect of daptomycin is the permeabilization and depolarization of the bacterial cell membrane. This activity, which can account for daptomycin's bactericidal effect, correlates with the level of phosphatidylglycerol (PG) in the membrane. Accordingly, reduced synthesis of PG or its increased conversion to lysyl-PG promotes bacterial resistance to daptomycin. While other resistance mechanisms suggest that daptomycin may indeed directly interfere with cell wall synthesis or cell division, such effects still await direct experimental confirmation. Daptomycin's complex structure and biosynthesis have hampered the analysis of its structure activity relationships. Novel methods of total synthesis, including a recent one that is carried out entirely on a solid phase, will enable a more thorough and systematic exploration of the sequence space.

show abstract

Section: Antimicrobial Spectrum and Clinical Usementioning

confidence: 99%

Section: Structure and Biosynthesismentioning

confidence: 99%

Section: Structure Of Tsushimycinmentioning

confidence: 99%

Section: Functional Effects Of Single or Combined Amino Acid Substitumentioning

confidence: 99%

“…Readers interested in learning more about these topics are referred to several previous reviews. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] …”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The action mechanism of daptomycin

Taylor

Palmer

2016

Bioorganic & Medicinal Chemistry

210

172

View full text Add to dashboard Cite

show abstract

Solid‐phase synthesis of fusaricidin/li‐f class of cyclic lipopeptides: Guanidinylation of resin‐bound peptidyl amines

2013

Self Cite

View full text Add to dashboard Cite

Fusaricidins/LI-Fs and related cyclic lipopeptides represent an interesting new class of antibacterial peptides with the potential to meet the challenge of antibiotic resistance in bacteria. Our previous study (N. Bionda et al. ChemMedChem 2012, 7, 871-882) revealed the significance of the guanidinium group located at the termini of the lipidic tails of these cyclic lipopeptides for their antibacterial activities. Therefore, devising a synthetic strategy that will allow incorporation of guanidinium functionality into their structure is of particular practical importance. Since appropriately protected guanidino fatty acid building blocks are not commercially available, our strategy toward guanidinylated fusaricidin/LI-F analogs include solid-phase synthesis of a cyclic lipopeptide precursor possessing a lipidic tail with a terminal amino group followed by its conversion into corresponding guanidine. To find the optimal method for this conversion, we have examined commonly used guanidinylation reagents under the conditions compatible with standard solid-phase peptide synthesis. Described experimental results demonstrated superiority of N,N′-di-Boc-N″-triflylguanidine in solid-phase preparation of fusaricidin/LI-F class of cyclic lipopeptides. The triflylguanidine reagent gave a single monoguanidinylated product in excellent yield independently of the type of solid-support.

show abstract

Ribosomal Synthesis of Natural‐Product‐Like Bicyclic Peptides in Escherichia coli

Bionda

Fasan

2015

ChemBioChem

Self Cite

View full text Add to dashboard Cite

Methods to access natural product-like macrocyclic peptides can disclose new opportunities for the exploration of this important structural class for chemical biology and drug discovery applications. Here, the scope and mechanism of a novel strategy for directing the biosynthesis of thioether-bridged bicyclic peptides in bacterial cells was investigated. This method entails split intein-catalyzed head-to-tail cyclization of a ribosomally produced precursor peptide combined with inter-side-chain cross-linking via a genetically encoded cysteine-reactive amino acid. This study demonstrates how this strategy can be successfully applied to achieve the formation of structurally diverse bicyclic peptides with high efficiency and selectivity in E. coli. Insights into the sequence of reaction underlying the peptide bicyclization process were gained from time course experiments. Finally, the potential utility of this methodology toward the discovery of macrocyclic peptides with enhanced functional properties was illustrated through the isolation of a bicyclic peptide with submicromolar affinity for streptavidin.

show abstract

Effects of Cyclic Lipodepsipeptide Structural Modulation on Stability, Antibacterial Activity, and Human Cell Toxicity

Cited by 53 publications

References 95 publications

The action mechanism of daptomycin

The action mechanism of daptomycin

Solid‐phase synthesis of fusaricidin/li‐f class of cyclic lipopeptides: Guanidinylation of resin‐bound peptidyl amines

Ribosomal Synthesis of Natural‐Product‐Like Bicyclic Peptides in Escherichia coli

Contact Info

Product

Resources

About