8dpy

Synthetic Beta Sheet Macrocycle Stabilized by Hydrogen Bond Surrogates

spinqualitylabelsall models 8dpy, resolution 1.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8dpy is a 2 chain structure with sequence from Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1Å Ligands: T7C, T7H Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Mimics of protein secondary and tertiary structure offer rationally-designed inhibitors of biomolecular interactions. beta-Sheet mimics have a storied history in bioorganic chemistry and are typically designed with synthetic or natural turn segments. We hypothesized that replacement of terminal inter-beta-strand hydrogen bonds with hydrogen bond surrogates (HBS) may lead to conformationally-defined macrocyclic beta-sheets without the requirement for natural or synthetic beta-turns, thereby providing a minimal mimic of a protein beta-sheet. To access turn-less antiparallel beta-sheet mimics, we developed a facile solid phase synthesis protocol. We surveyed a dataset of protein beta-sheets for naturally observed interstrand side chain interactions. This bioinformatics survey highlighted an over-abundance of aromatic-aromatic, cation-pi and ionic interactions in beta-sheets. In correspondence with natural beta-sheets, we find that minimal HBS mimics show robust beta-sheet formation when specific amino acid residue pairings are incorporated. In isolated beta-sheets, aromatic interactions endow superior conformational stability over ionic or cation-pi interactions. Circular dichroism and NMR spectroscopies, along with high-resolution X-ray crystallography, support our design principles. Macrocyclic beta-Sheets Stabilized by Hydrogen Bond Surrogates.,Nazzaro A, Lu B, Sawyer N, Watkins AM, Arora PS Angew Chem Int Ed Engl. 2023 Oct 9;62(41):e202303943. doi: , 10.1002/anie.202303943. Epub 2023 Jun 2. PMID:37170337 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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