Conformational domino: How coupled structural changes control macrocycle behavior
- grebner0
- Dec 1
- 1 min read
A new study published in the Journal of Medicinal Chemistry sheds light on how conformational changes in macrocycles are tightly coupled and propagated in a domino-like cascade, ultimately governing their overall behavior.
This multi-institutional effort brought together PROXIDRUGS members from TU Darmstadt, Fraunhofer ITMP, and AbbVie, alongside collaborators from ETH Zurich and the Max Planck Institute in Munich, combining complementary experimental and computational expertise. The researchers show how local conformational changes can trigger a cascade of structural rearrangements, providing new mechanistic insights into the dynamic behavior of macrocyclic compounds.
Understanding such conformational coupling is highly relevant for the rational design of advanced therapeutic modalities, including proximity-inducing drugs, where molecular flexibility and structural adaptability play a key role in function and selectivity.
