Lasso Peptides: Exploring the Folding Landscape of Nature's Smallest Interlocked Motifs.

ABSTRACT: Lasso peptides make up a class of natural products characterized by a threaded structure. Given their small size and stability, chemical synthesis would offer tremendous potential for the development of novel therapeutics. However, the accessibility of the pre-folded lasso architecture has limited this advance. To better understand the folding process de novo, simulations are used herein to characterize the folding propensity of microcin J25 (MccJ25), a lasso peptide known for its antimicrobial properties. New algorithms are developed to unambiguously distinguish threaded from nonthreaded precursors and determine handedness, a key feature in natural lasso peptides. We find that MccJ25 indeed forms right-handed pre-lassos, in contrast to past predictions but consistent with all natur

SUBMITTER: da Hora GCA 

PROVIDER: S-EPMC11282585 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature