MEMBRANE PEPTIDE STRUCTURE VIA NMR & QUANTUM CHEMISTRY

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The SIR provided L-[2- 13 C]Tryptophan; 2g L-13- 13C]Tryptophan; 1.25g The idea behind this project is to make 13C-labeled gramicidins, as prototypical membrane penetrating peptide/protein fragments, and to explore their structure using the ISOTROPIC CARBON- 13 CHEMICAL SHIF'F, plus quantum chemistry, as a probe of structure. Previous work has always focused on orientational (15N, 2H, some 13C) information - the position of a line in an oriented sample, rather than completely analyzing chemical shifts using quantum chemistry, which is what we propose here. The ability to analyze isotropic chemical shifts in proteins in structural terms has a good chance of making may more systems amenable to investigation, and Ca, Cb, Cg of Trp in gramicidin should be excellent probes (especially since the Trps are functionally significant). By combining the observed isotropic chemical shifts with the quantum chemically computed shielding surfaces, one obtains for Trp the solutions for c 1, c2 as well as f, y, c 1 results for Val, Leu. These unique solutions remove problems associated with may dipolar or quadrupolar derived geometry restraints, ans when combined with the often more accurate (but multivalued) tensor data should yield very accurate, unique NMR solutions, for f, y, c I, c2. Knowledge of Trp orientations is important for understanding gramicidin action, and the above results (together) with those we are planning to obtain with commercially available 13C glycines and alanines) should together clearly indicate the utility of chemical shifts in structure studies, especially since the chemical shift is, in a sense, the most fundamental NMR property.