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Front Cover: Towards Tuneable Retaining Glycosidase‐Inhibiting Peptides by Mimicry of a Plant Flavonol Warhead (ChemBioChem 23/2017)
Author(s) -
Yoshisada Ryoji,
van Gijzel Lieke,
Jongkees Seino A. K.
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700601
Subject(s) - warhead , peptide , chemistry , front cover , stereochemistry , folding (dsp implementation) , combinatorial chemistry , biochemistry , cover (algebra) , mechanical engineering , electrical engineering , engineering , aerospace engineering
The front cover picture shows a lariat noncanonical peptide scaffold presenting one half of a natural‐product‐derived warhead to human pancreatic α‐amylase. The folding of this peptide into an unusually stable 3 10 helix in solution is driven by a templating effect from the macrocyclic portion on the linear tail. This allows the peptide to place an l ‐DOPA side chain in such a way that it forms a strong chelate interaction with one of the enzyme's catalytic carboxylate groups. The resulting nonapeptide inhibitor has remarkable potency, with K i =480 p m . As the placement of catalytic carboxylates is conserved across all retaining glycosidases, if both halves of this warhead could be incorporated into such a peptide scaffold in the correct folded orientation, then the resulting inhibitor should be active across this class of enzymes. Its specificity could be tuned by varying the peptide side chains. More information can be found in the full paper by S. A. K. Jongkees et al. on page 2333 in Issue 23, 2017 (DOI: 10.1002/cbic.201700457).