7OS8

NMR SOLUTION STRUCTURE OF [Pro3,DLeu9]TL

Summary for 7OS8

• Entry DOI: 10.2210/pdb7os8/pdb
• NMR Information: BMRB: 34632
• Descriptor: PHE-VAL-PRO-TRP-PHE-SER-LYS-PHE-DLE-GLY-ARG-ILE-LEU-NH2 (1 entity in total)
• Functional Keywords: conformational analysis, antimicrobic, antimicrobial protein
• Biological source: Rana temporaria
• Total number of polymer chains: 1
• Total formula weight: 1609.98

Authors

Brancaccio, D.,Carotenuto, A. (deposition date: 2021-06-08, release date: 2021-08-11, Last modification date: 2024-10-09)

Primary citation

Bellavita, R.,Casciaro, B.,Di Maro, S.,Brancaccio, D.,Carotenuto, A.,Falanga, A.,Cappiello, F.,Buommino, E.,Galdiero, S.,Novellino, E.,Grossmann, T.N.,Mangoni, M.L.,Merlino, F.,Grieco, P.
First-in-Class Cyclic Temporin L Analogue: Design, Synthesis, and Antimicrobial Assessment.
J.Med.Chem., 64:11675-11694, 2021

PubMed Abstract: The pharmacodynamic and pharmacokinetic properties of bioactive peptides can be modulated by introducing conformational constraints such as intramolecular macrocyclizations, which can involve either the backbone and/or side chains. Herein, we aimed at increasing the α-helicity content of temporin L, an isoform of an intriguing class of linear antimicrobial peptides (AMPs), endowed with a wide antimicrobial spectrum, by the employment of diverse side-chain tethering strategies, including lactam, 1,4-substituted [1,2,3]-triazole, hydrocarbon, and disulfide linkers. Our approach resulted in a library of cyclic temporin L analogues that were biologically assessed for their antimicrobial, cytotoxic, and antibiofilm activities, leading to the development of the first-in-class cyclic peptide related to this AMP family. Our results allowed us to expand the knowledge regarding the relationship between the α-helical character of temporin derivatives and their biological activity, paving the way for the development of improved antibiotic cyclic AMP analogues.

PubMed: 34296619
DOI: 10.1021/acs.jmedchem.1c01033

Experimental method

SOLUTION NMR