Related Experiment Video
Updated: Aug 6, 2026

Universal Molecular Retention with 11-Fold Expansion Microscopy
Published on: October 6, 2023
Solution Ensembles of Griselimycin Expand the Definition of Molecular Chameleonicity
Luca J Hagemeyer1, William T P Darling1,2, Nele-Johanna Hempel-Højgaard3
1Department of Chemistry for Life Sciences, Uppsala University, UppsalaSE 751 23, Sweden.
Abstract:
Achieving satisfactory permeability for beyond the rule of 5 (bRo5) molecules, such as bioactive macrocycles, remains a challenge for drug discovery. Gaining a mechanistic understanding of the correlation between their structure and permeability is expected to improve the foundation for rational prediction of the pharmacokinetic behavior of novel macrocyclic drug candidates. Based on a solution-phase NMR investigation, we suggest that griselimycin, a macrocyclic peptide that has remarkable antibiotic activity, permeates membranes while exposing its polar moieties in an apolar membrane-like environment and hiding them in a polar environment. This noncanonical behavior is driven by the simultaneous exposure of lipophilic moieties in an apolar environment and by their hydrophobic collapse in aqueous solution. The unexpected behavior of griselimycin opposes the concept of classical chameleonicity and may be described as "inverse chameleonicity".
Related Concept Videos
Molecules with Multiple Chiral Centers
Chirality in Nature
Stereoisomerism of Cyclic Compounds
Stereoisomerism
Isomers are different chemical species that have the same chemical formula.
Transition metal complexes often exist as geometric isomers, in which the same atoms are connected through the same types of bonds but with differences in their orientation in space. Coordination complexes with two different ligands in the cis and trans positions from a ligand of interest form isomers. For example, the octahedral [Co(NH3)4Cl2]+ ion has two isomers (Figure 1) In the cis...
Racemic Mixtures and the Resolution of Enantiomers
Prochirality

