Synthesis of Cyclic Peptidotriazoles with Activity Against Phytopathogenic Bacteria

Güell, Imma; Vila, Silvia; Micaló, Lluís; Badosa, Esther; Seguí, Emilio Montesinos; Planas, Marta; Feliu, Lidia

doi:10.1002/ejoc.201300215

Cited by 13 publications

(25 citation statements)

References 36 publications

(13 reference statements)

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“…syringae (MIC of 1.6 to 12.5 μM), low hemolytic (0–23% at 50 μM), and no phytotoxic. Recently, we described the synthesis of cyclic peptidotriazoles derived from the antimicrobial cyclic peptide c(Lys‐Lys‐Leu 3 ‐Lys‐Lys 5 ‐Phe‐Lys‐Lys‐Leu‐Gln) ( BPC194 ) . These sequences were designed by incorporating a triazolyl amino acid at the 3‐position.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and biological evaluation of cyclic peptidotriazoles derived from BPC194 as novel agents for plant protection

et al. 2017

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The search for novel antimicrobial agents to be used for plant protection has prompted us to design analogues incorporating non-natural amino acids. Herein, we designed and synthesized cyclic peptidotriazoles derived from the lead antimicrobial cyclic peptide c(Lys-Lys-Leu -Lys-Lys -Phe-Lys-Lys-Leu-Gln) (BPC194). In particular, Leu and Lys were replaced by a triazolyl alanine, a triazolyl norleucine or a triazolyl lysine. These peptides were screened for their antibacterial activity against Xanthomonas axonopodis pv. vesicatoria, Erwinia amylovora, and Pseudomonas syringae pv. syringae, for their hemolysis and for their phytotoxicity. Results showed that the type of triazolyl amino acid and the substituent present at the triazole influenced the antibacterial and hemolytic activities. Moreover, the position of this residue was also crucial for the hemolysis. The lead compounds BPC548 and BPC550 exhibited high antibacterial activity (MIC of 3.1 to 25 μM), low hemolysis (19 and 26% at 375 μM, respectively) and low phytotoxicity. Therefore, these analogues could be used as new leads for the development of effective agents to control pathogenic bacteria responsible for plant diseases of economic importance.

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Section: Introductionmentioning

confidence: 99%

Design, synthesis, and biological evaluation of cyclic peptidotriazoles derived from BPC194 as novel agents for plant protection

et al. 2017

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“…This Leu 3 residue was selected because the cationic Lys residues and the fragment Lys 5 -Phe-Lys-Lys-Leu-Gln 10 have been shown to be essential for the antimicrobial activity of BPC194.…”

Section: Design Of the Peptide Conjugatesmentioning

confidence: 99%

“…7.95 94 Fmoc-Leu-Leu-Ile-Leu-Nle(ε-N 3 )-Tyr-Leu-NH 2 (8) 10.55 88 Fmoc-Leu-Phe-Lys-Lys-Ile-Leu-Nle(ε-N 3 )-Tyr-Leu-NH 2 (9) 8.54 94 Fmoc-Leu-Phe-Leu-Lys-Ile-Leu-Nle(ε-N 3 )-Tyr-Leu-NH 2 (10) 10.14 90 Fmoc-Lys-Lys-Leu-Phe-Lys-Lys-Ile-Leu-Nle(ε-N 3 )-Tyr-Leu-NH 2 (11) 7.76 95 Fmoc-Lys-Nle(ε-N 3 )-Leu-Phe-Lys-Lys-Ile-Leu-Lys-Tyr-Leu-NH 2 (12) 7.48 95 (13) 7.91 94 5.00 84…”

Section: Synthesis Of the Cyclic Alkynyl-peptidyl Resins 1-3unclassified

“…[9] In our efforts to find new antimicrobial agents, in a previous study we designed peptidotriazoles derived from the antimicrobial cyclic decapeptide c(Lys-Lys-Leu 3 -Lys-LysPhe-Lys-Lys-Leu-Gln) (BPC194) by incorporating a 1,2,3-triazole into the side-chain of the residue at the 3-position. [10] Peptidotriazoles were synthesized by a cycloaddition reaction between an alkynyl or azido resin and an azide or an alkyne in solution, respectively. A peptide conjugate was also prepared by linking an alkynyl resin derived from BPC194 and an azidopentapeptide through a triazolyl moiety.…”

Section: Introductionmentioning

confidence: 99%

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Solid‐Phase Synthesis of Peptide Conjugates Derived from the Antimicrobial Cyclic Decapeptide BPC194

et al. 2015

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The solid-phase conjugation of the antimicrobial peptide c(KKLKKFKKLQ) (BPC194) to a linear or cyclic sequence through a 1,2,3-triazole ring is described. Cyclic alkynyl-peptidyl resins derived from BPC194 were treated with azidopeptides derived from the antimicrobial peptide BP100 or from the bacteriocin iturin A. The cyclic alkynyl-peptidyl resins incorporated at the 3-position a propargylglycine, a glutamic acid residue derivatized with propargylamine or a lysine bearing a propioloyl group. The reactions of the cyclic alkynyl resins with the BP100-derived azidopeptides depended on the length and the sequence of the azidopeptides. The reactions were performed by treatment of the alkynyl resin with CuI and ascorbic acid, and required the presence of piperidine/DMF or DIEA in 2,6-lutidine/DMF. The latter conditions also allowed the conjugation of the alkynyl-peptidyl resin bearing a propioloyl lysine to a linear or cyclic azidopeptide derived from the cyclic moiety of iturin AS. V. was recipient of a predoctoral fellowship from the Generalitat de Catalunya. This work was supported by the Spanish Ministerio de Economia y Competitividad (MINECO) (grant numbers AGL2009-13255-C02-02/AGR and AGL2012-39880-C02-02

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“…In a large number of papers the affinity of α V β 3 integrin have been prepared to improve pharmacological properties [10][11][12][13][14][15] and to investigate new materials. 16,17 Amide-linked units form most of these peptides, while some incorporate unnatural linkages.…”

Section: Introductionmentioning

confidence: 99%

Orthogonal Protection of Peptides and Peptoids for Cyclization by the Thiol–Ene Reaction and Conjugation

2014

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Abstract/TOC graphic AbstractCyclic peptides and peptoids were prepared using the thiol-ene Michael-type reaction.The linear precursors were provided with additional functional groups allowing for subsequent conjugation: an orthogonally protected thiol, a protected maleimide, or an alkyne. The functional group for conjugation was placed either within the cycle or in an external position. The click reactions employed for conjugation with suitably derivatized nucleoside or oligonucleotides were either cycloadditions (Diels-Alder, Cu(I)-catalyzed azide-alkyne) or the same Michael-type reaction as for cyclization.

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Synthesis of Cyclic Peptidotriazoles with Activity Against Phytopathogenic Bacteria

Cited by 13 publications

References 36 publications

Design, synthesis, and biological evaluation of cyclic peptidotriazoles derived from BPC194 as novel agents for plant protection

Design, synthesis, and biological evaluation of cyclic peptidotriazoles derived from BPC194 as novel agents for plant protection

Solid‐Phase Synthesis of Peptide Conjugates Derived from the Antimicrobial Cyclic Decapeptide BPC194

Orthogonal Protection of Peptides and Peptoids for Cyclization by the Thiol–Ene Reaction and Conjugation

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