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Aminoquinoline-Rhodium(II) Conjugates as Src-Family SH3 Ligands.

ABSTRACT: High-affinity, selective ligands are sought for a variety of biomolecules but are particularly difficult to generate in the protein-protein interaction space. Rhodium(II) conjugates provide a structure-based approach to improved affinity and specificity for targeting protein-protein interactions such as SH3 domains. In this study of small-molecule-rhodium conjugates, we report a potent ligand 4b (K d of 27 nM) for the Lyn SH3 domain, based on an aminoquinoline fragment. The results demonstrate robust affinity gains possible from even modest small-molecule leads through cooperative inorganic-organic binding, based on specific histidine interactions. A docking study sheds light on the structural basis of binding and supports a previously proposed binding model.

SUBMITTER: Martin SC

PROVIDER: S-EPMC6792148 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Aminoquinoline-Rhodium(II) Conjugates as Src-Family SH3 Ligands.

Martin Samuel C SC Ball Zachary T ZT

ACS medicinal chemistry letters 20190909 10

High-affinity, selective ligands are sought for a variety of biomolecules but are particularly difficult to generate in the protein-protein interaction space. Rhodium(II) conjugates provide a structure-based approach to improved affinity and specificity for targeting protein-protein interactions such as SH3 domains. In this study of small-molecule-rhodium conjugates, we report a potent ligand 4b (K d of 27 nM) for the Lyn SH3 domain, based on an aminoquinoline fra ...[more]

PMID: 31620222

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