Ontology highlight
ABSTRACT:
SUBMITTER: Gradler U
PROVIDER: S-EPMC7195332 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
Bioorganic & medicinal chemistry letters 20191016 23
Fragment-based screening by SPR enabled the discovery of chemical diverse fragment hits with millimolar binding affinities to the peptidyl-prolyl isomerase Cyclophilin D (CypD). The CypD protein crystal structures of 6 fragment hits provided the basis for subsequent medicinal chemistry optimization by fragment merging and linking yielding three different chemical series with either urea, oxalyl or amide linkers connecting millimolar fragments in the S1' and S2 pockets. We successfully improved t ...[more]