Structure of a hydrophobic leucinostatin derivative determined by host lattice display

Acta Crystallogr D Struct Biol. 2022 Dec 1;78(Pt 12):1439-1450. doi: 10.1107/S2059798322010762. Epub 2022 Nov 29.


Peptides comprising many hydrophobic amino acids are almost insoluble under physiological buffer conditions, which complicates their structural analysis. To investigate the three-dimensional structure of the hydrophobic leucinostatin derivative ZHAWOC6027, the previously developed host lattice display technology was applied. Two designed ankyrin-repeat proteins (DARPins) recognizing a biotinylated ZHAWOC6027 derivative were selected from a diverse library by ribosome display under aqueous buffer conditions. ZHAWOC6027 was immobilized by means of the DARPin in the host lattice and the structure of the complex was determined by X-ray diffraction. ZHAWOC6027 adopts a distorted α-helical conformation. Comparison with the structures of related compounds that have been determined in organic solvents reveals elevated flexibility of the termini, which might be functionally important.

Keywords: crystal engineering; host lattice display; leucinostatins.

MeSH terms

  • Amino Acids*
  • Antimicrobial Cationic Peptides*
  • Ribosomes
  • X-Ray Diffraction


  • leucinostatin A
  • Antimicrobial Cationic Peptides
  • Amino Acids