Unique amalgamation of primary and secondary structural elements transform peptaibols into potent bioactive cell-penetrating peptides.

ABSTRACT: Mass-spectrometry-based metabolomics and molecular phylogeny data were used to identify a metabolically prolific strain of Tolypocladium that was obtained from a deep-water Great Lakes sediment sample. An investigation of the isolate's secondary metabolome resulted in the purification of a 22-mer peptaibol, gichigamin A (1). This peptidic natural product exhibited an amino acid sequence including several β-alanines that occurred in a repeating ααβ motif, causing the compound to adopt a unique right-handed 3₁₁ helical structure. The unusual secondary structure of 1 was confirmed by spectroscopic approaches including solution NMR, electronic circular dichroism (ECD), and single-crystal X-ray diffraction analyses. Artificial and cell-based membrane permeability assays

SUBMITTER: Du L 

PROVIDER: S-EPMC5664515 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature