6b35

NMR ensemble of Tyrocidine A analogue AC3.28

spinqualitylabelsall models 6b35 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6b35 is a 1 chain structure with sequence from Brevibacillus brevis. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Ligands: BE2, DPN, ORN, PRD_002290 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The d-Phe-Pro beta-turn of the cyclic beta-hairpin antimicrobial decapeptide tyrocidine A, (Tyrc A) was substituted with the d-Phe-2-aminobenzoic acid (2-Abz) motif in a synthetic analogue (1). The NMR structure of 1 demonstrated that compound 1 retained the beta-hairpin structure of Tyrc A with additional planarity, resulting in approximately 30-fold reduced hemolysis than Tyrc A. Although antibacterial activity was partially compromised, a single Gln to Lys substitution (2) restored activity equivalent to Tyrc A against S. aureus, enhanced activity against two Gram negative strains and maintained the reduced hemeloysis of 1. Analysis by transmission electron microscopy (TEM) suggested a membrane lytic mechanism of action for these peptides. Compound 2 also exhibits nanomolar antifungal activity in synergy with amphotericin B. The d-Phe-2-Abz turn may serve as a tool for the synthesis of structurally predictable beta-hairpin libraries. Unlike traditional beta-turn motifs such as d-Pro-Gly, both the 2-Abz and d-Phe rings may be further functionalized. Tyrocidine A Analogues Bearing the Planar d-Phe-2-Abz Turn Motif: How Conformation Impacts Bioactivity.,Cameron AJ, Edwards PJB, Harjes E, Sarojini V J Med Chem. 2017 Nov 28. doi: 10.1021/acs.jmedchem.7b00953. PMID:29140694 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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