DETERMINATION OF INDIVIDUAL SIDE-CHAIN CONFORMATIONS, TERTIARY CONFORMATIONS, AND MOLECULAR TOPOGRAPHY OF TYROCIDINE-A FROM SCALAR COUPLING-CONSTANTS AND CHEMICAL-SHIFTS

We report for the decapeptide tyrocidine A: (a) Hα and Hβ chemical shifts and scalar coupling constants for most residues of tyrocidine A in methanol-d4 and dimethyl-d6 sulfoxide (Me2SO-d6) and the Hα and Hβ chemical shifts for other residues; (b) scalar coupling constants 3Jαβ for nine side chains in methanol-d4 but only seven side chains in Me2SO-d6, due to chemical shift degeneracy; the G1n9 and Tyr10 side chains in methanol-d4 were only approximately analyzed; (c) a total spin-spin analysis of Pro5 in Me2SO-d6 and, partly by comparison, also in methanol-d4; (d) conversion of 3Jαβ values to side-chain conformations for all residues in methanol-d4; comparisons, where possible, led to the conclusion that side-chain conformations are similar in methanol-d4 and Me2SO-d6; (e) an absolute conformational analysis of Pro5 from 3J values and a method of assigning all pro-R,S protons; Pro5 has a Ramachandran B, C2-Cexo-Cendo conformation; (f) χ1.χ2@r@nconformations of several aromatic residues based upon proton-chromophore distance measurement from anomalous chemical shifts and Johnson-Bovey diagrams; (g) pro-R and pro-S assignments of Hβs from anomalous chemical shifts, high-temperature dependence of anomalous chemical shifts, and backbone side-chain nuclear Overhauser effects; (h) most tertiary conformations of the whole tyrocidine A molecule possessing residues 4-8 and 10 in highly preferred (ca. 90%) χ1 conformations, but residues 1-3 and 9 having at least two χ1 rotamers; (i) description of three topographical regions of the molecule—a hydrophobic region, a flat hydrophilic surface on the other side of the molecule, and a hydrophilic region consisting of two peptide backbone units and the side chains of Asn8, G1n9, and Tyr10; (j) proposed side chain, β-turn, and β-pleated sheet conformations that readily account for all “normal” and anomalous chemical shifts. © 1979, American Chemical Society. All rights reserved.