Macrocyclic compounds (MCs) can have complex conformational properties that affect
pharmacologically important behaviors such as membrane permeability. We measured the …

Compounds beyond the rule-of-five are generating interest as they expand the molecular
toolbox for modulating targets previously considered “undruggable”. Macrocyclic peptides …

Incorporating small modifications to peptidic macrocycles can have a major influence on
their properties. For instance, N-methylation has been shown to impact permeability. A better …

Macrocycles are of increasing interest as chemical probes and drugs for intractable targets
like protein–protein interactions, but the determinants of their cell permeability and oral …

Many cyclic peptide natural products are larger and structurally more complex than
conventional small molecule drugs. Although some molecules in this class are known to …

We herein report the first thorough analysis of the structure–permeability relationship of
semipeptidic macrocycles. In total, 47 macrocycles were synthesized using a hybrid solid …

Passive membrane permeability is a fundamental challenge in the development of bioactive
macrocycles. To achieve this objective, chemists have resorted to various strategies, the …

Conformation-dependent 3D descriptors have been shown to provide better predictions of
the physicochemical properties of macrocycles than 2D descriptors. However, the …

Macrocycles constitute superior ligands for targets that have flat binding sites but often
require long synthetic routes, emphasizing the need for property prediction prior to …

Large macrocyclic peptides can achieve surprisingly high membrane permeability, although
the properties that govern permeability in this chemical space are only beginning to come …