STRUCTURE DETERMINATION OF RACEMIC TRICHOGIN-A-IV USING CENTROSYMMETRIC CRYSTALS

Direct methods of crystal structure solution are greatly facilitated i n centrosymmetric space groups where the complexity of the phase-probl em is reduced. For most peptides and proteins, crystallization in a ce ntrosymmetric arrangement is precluded by an intrinsic dissymmetry due to the constituent chiral amino acid residues. The synthetic accessib ility of peptide sequences containing amino acids of either chirality offers the possibility for cocrystallization of racemic crystals. We r eport here the first use of such an approach for the de novo structure determination of a medium-sized molecule, trichogin A IV, which is a constituent of a fungal lipopeptaibol mixture possessing membrane-modi fying properties of biological interest.