The aim in the proposed research is to determine the three- dimensional structure (by x-ray diffraction of single crystals) of a number of peptides (10-30 residues) that perform a variety of functions such as ion transport, analgesia, toxic, antitoxic, and antibiotic by means of single crystal x-ray diffraction analysis. These crystals are composed of molecules containing light atoms only, C, N, O and H. The method of solution will be direct phase determination using the tangent formula and a variety of auxiliary formulas. Linear peptides mediating ion transport through cell membranes, particularly those in the class of peptaibophol antibiotics, are being emphasized currently. They are characterized by their length (up to 20 residues), a number of Aib residues (alpha aminoisobutyric acid) and one or more Pro residues that interfere with alpha-helix formation. The immediate goal is to establish the conformation of neighboring peptide molecules in the crystal. The ultimate goal is to determine modes of aggregation that form ion channels in membranes. The specific peptide structures that are being studied and will continue to be studied are polymorphs of 10-residue apolar analogs of zervamicin II; the 16-residue antiamoebin; Boc(Aib- Ala-Leu)3-Aib-OMe, a 10-residue fragment of an ion transport peptide; Boc-Cys-Val-Aib-Ala-Leu-Cys-NHMe; and others, including the continuation of structure analyses of gramicidin A, a dodecapeptide from elastin, and a new conformation for uncomplexed valinomycin from a very polar solvent.
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