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7989 essential imidazolium to the unstable tetrahedral intermediates produced from amides where the N is an aliphatic one, the proton transfer is thermodynamically favorable, and in the case of anilides is either thermodynamically neutral or only slightly uphill.The second and less obvious feature of imidazole which makes it unusually suitable for general-acid or -base catalysis relative to an aliphatic amine (ammonium) has to do with the molecular shape. Because the proton transfer in imidazole occurs at the sp2 N, and in the plane of the ring, there is minimal steric hindrance in transfer to sterically congested tetrahedral intermediates.Acknowledgment. The authors gratefully acknowledge the financial support of the University of Alberta and the Natural Sciences and Engineering Research Council of Canada. In addition, J.K. acknowledges NSERC for a Post Graduate Scholarship.Supplementary Material Available: Tables of observed rate constants vs pH for attack of thiols lb, 5 a 4 , and 6a-d on amide 4 and characterization of thiol ester 8b and amide 9a (7 pages). Ordering information is given on any current masthead page. Abstract:The structural determination of modified nucleosides is important for understanding the chemistry, structure, and functional changes that they introduce to the nucleic acids in which they occur. Thiolation of transfer RNA wobble position undine produces an energetically stabilized conformation of the nucleoside in solution at ambient temperature that is independent of the nature of the 5-position substituent and is of biological significance to tRNA selection of only those codons ending in adenosine (Sierzputowska-Gracz, H.; Sochacka, E.; Malkiewicz, A.; Kuo, K.; Gehrke, C.; Agris, P. F. J . Am. Chem. SOC. 1987, 109, 7171-7177. Agris, P. F.; Sierzputowska-Gracz, H.; Smith, W.; Malkiewicz, A.; Sochacka, E.; Nawrot, B. J. Am.Chem. Soc., in press). Dinucleoside monophosphates have been synthesized as models for investigating the conformations and structures of wobble position uridine-34 that is thiolated and differently modified at position-5 and that is either 3'-adjacent to the invariant uridine-33 in tRNA or 5'-adjacent to the second anticodon position uridine-35. The structures and conformations of 11 dinucleoside monophosphates were analyzed by IH, I3C, and magnetic resonance (NMR) spectroscopy. Within the dinucleosides, the individual modified uridine structures and conformations were very similar to those of their respective mononucleosides. The 2-position thiolation, and not the 5-position modification, produced a significantly more stable, C(3') endo, gauche+, anti conformer. However, within those dinucleosides in which the 2-thiouridine was 5' to the unmodified uridine, the nucleic acid backbone torsion angles of the unmodified uridine 5'-phosphate were affected, as determined from the scalar coupling constants JiHiH, JiH"p, and J13~31p. In contrast, uridines that were only 5-position modified did not affect the conformation of the 3'-adjacent unmodified uridine phosphate. The stru...

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The receptor binding surface of human follicle-stimulating hormone (hFSH) is mimicked by synthetic peptides corresponding to the hFSH-beta chain amino acid sequences 33-53 [Santa-Coloma, T. A., Dattatreyamurty, D., and Reichert, L. E., Jr. (1990), Biochemistry 29, 1194-1200], 81-95 [Santa-Coloma, T. A., Reichert, L. E., Jr. (1990), J. Biol. Chem. 265, 5037-5042], and the combined sequence (33-53)-(81-95) [Santa-Coloma, T. A., Crabb, J. W., and Reichert, L. E., Jr. (1991), Mol. Cell. Endocrinol. 78, 197-204]. These peptides have been shown to inhibit binding of hFSH to its receptor. Circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy were used to determine the structure of the first peptide in this series, the 21 amino acid peptide hFSH-beta-(33-53), H2N-YTRDLVYKDPARPKIQKTCTF-COOH. Analysis of CD data indicated the presence of approximately equal amounts of antiparallel beta-pleated sheet, turns including a beta-turn, "other" structures, and a small amount of alpha-helix. The major characteristics of the structure were found to be relatively stable at acidic pH and the predominant effect of increased solvent polarity was a small increase in alpha-helical content. One- and two-dimensional NMR techniques were used to obtain full proton and carbon signal assignments in aqueous solution at pH 3.1. Analysis of NMR results confirmed the presence of the structural features revealed by CD analysis and provided a detailed picture of the secondary structural elements and global folding pattern in hFSH-beta-(33-53). These features included an antiparallel beta-sheet (residues 38-51 and 46-48), turns within residues 41-46, and 50-52 (a beta-turn) and a small N-terminal helical region comprised of amino acids 34-36. One of the turns is facilitated by prolines 42 and 45. Proline-45 was constrained to the trans conformation, whereas proline-42 favored the trans conformer (approximately 70%) over the cis (approximately 30%). Two resonances were observed for the single alanine residue (A-43) sequentially proximal to P-42, but the rest of the structure was minimally affected by the isomerization at proline-42. The major population of molecules, containing trans-42 and trans-45 prolines, presented 120 NOEs. Distance geometry calculations with 140 distance constraints and energy minimization refinements were used to derive a moderately well-defined model of the peptide's structure.(ABSTRACT TRUNCATED AT 400 WORDS)