Design Of Synthetic Routes Research Articles

The β-Sheet Structure-Stabilizing Potential of Twenty Kinds of Amino Acid Residues in Protected Peptides

Abstract A host–guest approach was devised to investigate the β-sheet structure-stabilizing potential of the 20 common amino acid residues in protected peptides where functional groups in side chains were protected by suitable groups commonly used in peptide synthesis. The potential was evaluated using solvent-titration curves for the disruption of the β-sheet structure of cross-linked polystyrene resin-bound host–guest hexa- and octapeptides in CH2Cl2 by HFIP. The β-sheet structure of host–guest hexapeptides, Boc–Val–Ile–X2–Val–Ile-NHCH2–resins, in which X stands for guest amino acid residues, was disrupted in CH2Cl2 by adding increasing amounts of HFIP; the disrupted behaviors were strongly dependent on the nature of guest amino acid residues. A scale for the β-sheet structure-stabilizing potential of the 20 kinds of amino acid residues in CH2Cl2 could be derived at 0.25 M of HFIP concentration as follows: Ile, Val>>Asn>His(Tos) or His, Gln, Cys(Bzl), Tyr(Bzl)>Phe, Gly, Lys(Z), Arg(Tos), Leu>Thr(Bzl), Ala, Met(O), Glu(OBzl), Trp(CHO)>>Ser(Bzl), Asp(OBzl)>>Pro. To confirm the scale, their β-sheet structure-stabilizing potential was further examined using host–guest octapeptides, Boc–X2–Val–Ile–X2–Val–Ile–NHCH2–resins. The disrupted behaviors of the octapeptides having Gly, Ala, and Thr(Bzl) residues as guests were remarkably different from those of the corresponding hexapeptides; the β-sheet structure-stabilizing potential of the Gly, Ala, and Thr(Bzl) residues became significantly high with an increase in their ratios to host residues. The potential of the Gly, Ala, and Thr(Bzl) residues appears to reflect the ratios of guest amino acid residues to hosts, the repeated sequence, and/or neighbor interactions in the sequence. The significance of the present study in the design of synthetic routes for peptides and proteins is briefly discussed.

Synthesis of Naturally Occurring C-Nucleosides, Their Analogs, and Functionalized C-Glycosyl Precursors

Publisher Summary The C-nucleosides are a group of C-glycosylated heterocycles in which the anomeric carbon atom is attached to the heterocycle by a C-C bond. C-nucleosides have been mainly from fermentation sources, and have been found to exhibit a variety of interesting biological properties. Pyrazomycin has significant antiviral activity. Formycin, formycin B, and oxazinomycins exhibit, in addition, antitumor activity. The biological importance of most of the naturally occurring C-nucleosides has prompted the exploration of synthetic routes leading to these compounds and their analogs. As synthetic targets, the C-nucleosides have deceptively simple structures, and the design of synthetic routes to them must take two important factors into account. Firstly, the methods selected for C-C bond formation at the anomeric center should be stereocontrolled because the structures known thus far are, with two exceptions, β-D-glycosyl compounds. Secondly, the carbon atom attached to the glycosyl group in a C-nucleoside precursor should be appropriately substituted or be amenable to substitution, so as to allow the elaboration of the other heterocyclic portion of the molecule.