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Functionalized Proline‐Rich Peptides Bind the Bacterial Second Messenger c‐di‐GMP
Author(s) -
Foletti Carlotta,
Kramer Rolf A.,
Mauser Harald,
Jenal Urs,
Bleicher Konrad H.,
Wennemers Helma
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201801845
Subject(s) - tetrapeptide , pentapeptide repeat , chemistry , second messenger system , peptide , biofilm , nucleotide , biochemistry , biology , bacteria , enzyme , genetics , gene
c‐di‐GMP is an attractive target in the fight against bacterial infections since it is a near ubiquitous second messenger that regulates important cellular processes of pathogens, including biofilm formation and virulence. Screening of a combinatorial peptide library enabled the identification of the proline‐rich tetrapeptide Gup‐Gup‐Nap‐Arg, which binds c‐di‐GMP selectively over other nucleotides in water. Computational and CD spectroscopic studies provided a possible binding mode of the complex and enabled the design of a pentapeptide with even higher binding strength towards c‐di‐GMP. Biological studies showed that the tetrapeptide inhibits biofilm growth by the opportunistic pathogen P. aeruginosa.