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Synthesis of Cyclic Peptidotriazoles with Activity Against Phytopathogenic Bacteria
Author(s) -
Güell Imma,
Vilà Sílvia,
Micaló Lluís,
Badosa Esther,
Montesinos Emilio,
Planas Marta,
Feliu Lidia
Publication year - 2013
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201300215
Subject(s) - chemistry , cycloaddition , cyclic peptide , peptide , combinatorial chemistry , antimicrobial , alkyne , solid phase synthesis , conjugated system , stereochemistry , peptide synthesis , antibacterial activity , azide , amino acid , in vitro , click chemistry , bacteria , organic chemistry , catalysis , biochemistry , polymer , biology , genetics
Abstract Cyclic peptidotriazoles derived from the antimicrobial cyclic peptide c(Lys‐Lys‐Leu‐Lys‐Lys‐Phe‐Lys‐Lys‐Leu‐Gln) (BPC194) were prepared by incorporating a triazolyl amino acid at the 3‐position. The synthesis was accomplished on solid‐phase and involved as the key step a copper‐catalyzed cycloaddition reaction between a resin‐bound alkyne or a resin‐bound azide and a range of azides or alkynes in solution, respectively. This methodology was also applied to the synthesis of a conjugated peptide containing a cyclic and a linear peptidyl sequence linked through a triazolyl ring. Cyclic peptidotriazoles were obtained in excellent purities starting either from an alkynyl or an azido peptidyl resin. These compounds were screened in vitro for their growth inhibition of bacterial phytopathogens and for their cytotoxic effects on eukaryotic cells. Peptide sequences with high antibacterial activity and low hemolysis were identified, constituting good candidates for the design of new antimicrobial agents.