6vxy

Triazole bridged SFTI1 inhibitor in complex with beta-trypsin

spinqualitylabelsall models 6vxy, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6vxy is a 2 chain structure with sequence from Bos taurus and Helianthus annuus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.398Å Ligands: CA, WMH Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TRY1_BOVIN Publication Abstract from PubMed Ruthenium-catalysed azide-alkyne cycloaddition (RuAAC) is an emerging tool for organic and medicinal chemistry that provides access to 1,5-disubstituted 1,2,3-triazole motifs for applications in peptide engineering. Despite its growing popularity, investigation of this motif as a disulfide mimetic in backbone cyclic peptides has been limited, and structural consequences remain to be studied. Here, we establish synthetic strategies to install various triazole linkages in cyclic peptides using backbone cyclisation and RuAAC cross-linking reactions. These linkages were evaluated in four serine protease inhibitors based on the sunflower trypsin inhibitor-1 framework. NMR and X-ray crystallography revealed exceptional consensus of bridging distance and backbone conformations (RMSD <0.5 A) of the triazole linkages when compared to the parent disulfide molecules. The triazole-bridged peptides displayed superior half-lives in liver S9 stability assays compared to disulfide-bridged peptides. This work establishes a strong foundation for the application of 1,5-disubstituted 1,2,3-triazoles as disulfide mimetics. Application and Structural Analysis of Triazole-Bridged Disulfide Mimetics in Cyclic Peptides.,White A, de Veer S, Wu G, Harvey P, Yap K, King GJ, Swedberg JE, Wang CK, Law RHP, Durek T, Craik D Angew Chem Int Ed Engl. 2020 Apr 8. doi: 10.1002/anie.202003435. PMID:32270580 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Trypsin 3D structures Trypsin inhibitor 3D structures

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