Importance of the Cyclic Cystine Knot Structural Motif for Immunosuppressive Effects of Cyclotides.

ABSTRACT: The cyclotide T20K inhibits the proliferation of human immune cells and is currently in clinical trials for multiple sclerosis. Here, we provide novel functional data and mechanistic insights into structure-activity relationships of T20K. Analogs with partial or complete reduction of the cystine knot had loss of function in proliferation experiments. Similarly, an acyclic analog of T20K was inactive in lymphocyte bioassays. The lack of activity of non-native peptide analogs appears to be associated with the ability of cyclotides to interact with and penetrate cell membranes, since cellular uptake studies demonstrated fast fractional transfer only of the native peptide into the cytosol of human immune cells. Therefore, structural differences between cyclic and linear native folded peptides

SUBMITTER: Hellinger R 

PROVIDER: S-EPMC9286316 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature