Cover Picture: Efficient Stacking on Protein Amide Fragments (ChemMedChem 3/2013). Issue 3 (22nd February 2013)

• Record Type: Journal Article
• Authors: Harder, Michael; Kuhn, Bernd; Diederich, François
• Is Part Of: ChemMedChem. Volume 8:Issue 3(2013:Mar.)
• Page Start: 345
• Page End: 345
• Publication Date: 2013-02-22
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201390005
• Languages: English
• ISSNs: 1860-7179

Abstract

<abstract abstract-type="graphical" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The noncovalent interaction between medicinal chemistry‐relevant heterocycles and protein amide groups was studied in detail in the Full Paper by Michael Harder, Bernd Kuhn, and Francois Diederich (<ext-link ext-link-type="doi" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">p. 397 ff.).</ext-link><bold>The front cover picture shows</bold> two examples of protein binding sites that expose backbone amides for ligand interaction: in the background, the extended beta sheet structure of an amyloid is shown, and in the top‐right, the solvent‐accessible surface of the active site of cathepsin L is displayed. The base of the S3 pocket, which is formed by a glycine‐containing dipeptide fragment of the cathepsin L backbone, is highlighted. To optimally exploit the interaction with such motifs in ligand design, guidelines are devised based on extensive quantum chemical calculations on various arene/amide dimers. Both a correlation of the interaction strength with the magnitude of the fragment dipole moment and a significant energetic preference for an antiparallel alignment of the interacting dipole vectors could be demonstrated.<boxed-text content-type="graphic" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgg1tstqk7h" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> </abstract>