Illuminating the Dark Conformational Space of Macrocycles Using Dominant Rotors
Andrei Yudin describes a method for isolating unique and previously understudied conformations of macrocycles.
Macrocycles can target complex protein interfaces that are not readily tractable through traditional small-molecule approaches. According to Professor Andrei Yudin from the University of Toronto (Canada) “the most significant and enabling feature of macrocyclic drugs and biological probes, in contrast to their small molecule counterparts, is perhaps their intricate three-dimensional shape, or conformation.” He continued: “Apart from relatively small rings such as cyclohexane, deciphering conformation–activity relationships in larger molecules is substantially more complicated. As a result, there is substantial interest in technologies that allow systematic studies of the effect of macrocyclic conformational changes on biological activity.”
In a recent paper, the Yudin group used the term ‘dark conformational space’ to describe the metastable states in peptide structures observed by NMR and X-ray crystallography.
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