6QXC

NMR structure of peptide 8, characterized by a trans-4-cyclohexyl-Pro, with a dramatic reduction in activity on E. coli ATCC and lost effect on P. aeruginosa.

Summary for 6QXC

• Entry DOI: 10.2210/pdb6qxc/pdb
• NMR Information: BMRB: 34367
• Descriptor: PHE-VAL-TCP-TRP-PHE-SER-LYS-PHE-LEU-GLY-ARG-ILE-LEU-NH2 (1 entity in total)
• Functional Keywords: temporins, antimicrobial, amps, proline derivatives, antibiotic
• Biological source: Pseudis bolbodactyla
• Total number of polymer chains: 1
• Total formula weight: 1692.12

Authors

Brancaccio, D.,Carotenuto, A.,Merlino, F.,Grieco, P.,Novellino, E. (deposition date: 2019-03-07, release date: 2019-05-29, Last modification date: 2024-11-13)

Primary citation

Buommino, E.,Carotenuto, A.,Antignano, I.,Bellavita, R.,Casciaro, B.,Loffredo, M.R.,Merlino, F.,Novellino, E.,Mangoni, M.L.,Nocera, F.P.,Brancaccio, D.,Punzi, P.,Roversi, D.,Ingenito, R.,Bianchi, E.,Grieco, P.
The Outcomes of Decorated Prolines in the Discovery of Antimicrobial Peptides from Temporin-L.
Chemmedchem, 14:1283-1290, 2019

PubMed Abstract: Previously, we identified a potent antimicrobial analogue of temporin L (TL), [Pro ]TL, in which glutamine at position 3 was substituted with proline. In this study, a series of analogues in which position 3 is substituted with non-natural proline derivatives, was investigated for correlations between the conformational properties of the compounds and their antibacterial, cytotoxic, and hemolytic activities. Non-natural proline analogues with substituents at position 4 of the pyrrolidine ring were considered. Structure-activity relationship (SAR) studies of these analogues were performed by means of antimicrobial and cytotoxicity assays along with circular dichroism (CD) and NMR spectroscopic analyses for selected compounds. The most promising peptides were additionally evaluated for their activity against some representative veterinary microbial strains to compare with those from human strains. We identified novel analogues with interesting properties that make them attractive lead compounds.

PubMed: 31087626
DOI: 10.1002/cmdc.201900221

Experimental method

SOLUTION NMR