High throughput evaluation of macrocyclization strategies for conformer stabilization.

ABSTRACT: While macrocyclization of a linear compound to stabilize a known bioactive conformation can be a useful strategy to increase binding potency, the difficulty of macrocycle synthesis can limit the throughput of such strategies. Thus computational techniques may offer the higher throughput required to screen large numbers of compounds. Here we introduce a method for evaluating the propensity of a macrocyclic compound to adopt a conformation similar that of a known active linear compound in the binding site. This method can be used as a fast screening tool for prioritizing macrocycles by leveraging the assumption that the propensity for the known bioactive substructural conformation relates to the affinity. While this method cannot to identify new interactions not present in the known linear c

SUBMITTER: Sindhikara D 

PROVIDER: S-EPMC5920116 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature