Backbone Alterations in Cyclic Peptides Influence Both Membrane Permeability and Biological Activity.

ABSTRACT: Cyclic peptides hold significant potential as disruptors of challenging targets such as protein-protein interactions, but their poor passive membrane permeability limits their use. In this study, we used a combination of cell-permeability assays and a target-agnostic cell-painting assay to observe how minimal structural changes affect membrane permeability and the biological activity of Sanguinamide A analogues. Significant differences in permeability were observed among the analogues, and for those that were permeable, NMR spectroscopy revealed conformational changes in response to environmental polarity. In the cell-painting assay, we observed that even though permeability generally correlated with overall morphological changes, distinct differences in specific activities were observed d

SUBMITTER: Openy J 

PROVIDER: S-EPMC12670408 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature