A Designed Three-Stranded beta-Sheet in an alpha/beta Hybrid Peptide

作者：Sonti Rajesh; Gopi Hosahudya N; Muddegowda Umashankara; Ragothama Srinivasarao; Balaram Padmanabhan^*

来源：Chemistry - A European Journal, 2013, 19(19): 5955-5965.

DOI：10.1002/chem.201204327

• amino acids
• hydrogen bonds
• NMR spectroscopy
• peptides
• structure elucidation

The incorporation of beta-amino acid residues into the antiparallel beta-strand segments of a multi-stranded beta-sheet peptide is demonstrated for a 19-residue peptide, Boc-LV(beta)FV(D)PGL(beta)FVVL(D)PGLVL(beta)FVV-OMe (BBH19). Two centrally positioned (D)Pro-Gly segments facilitate formation of a stable three-stranded beta-sheet, in which beta-phenylalanine ((beta)Phe) residues occur at facing positions 3, 8 and 17. Structure determination in methanol solution is accomplished by using NMR-derived restraints obtained from NOEs, temperature dependence of amide NH chemical shifts, rates of H/D exchange of amide protons and vicinal coupling constants. The data are consistent with a conformationally well-defined three-stranded beta-sheet structure in solution. Cross-strand interactions between (beta)Phe3/(beta)Phe17 and (beta)Phe3/Val15 residues define orientations of these side-chains. The observation of close contact distances between the side-chains on the N- and C-terminal strands of the three-stranded beta-sheet provides strong support for the designed structure. Evidence is presented for multiple side-chain conformations from an analysis of NOE data. An unusual observation of the disappearance of the Gly NH resonances upon prolonged storage in methanol is rationalised on the basis of a slow aggregation step, resulting in stacking of three-stranded beta-sheet structures, which in turn influences the conformational interconversion between type I%26apos; and type II%26apos; beta-turns at the two (D)Pro-Gly segments. Experimental evidence for these processes is presented. The decapeptide fragment Boc-LV(beta)FV(D)PGL(beta)FVV-OMe (BBH10), which has been previously characterized as a type I%26apos; beta-turn nucleated hairpin, is shown to favour a type II%26apos; beta-turn conformation in solution, supporting the occurrence of conformational interconversion at the turn segments in these hairpin and sheet structures.

• 出版日期2013-5