Yanwen Fu

A 310-helical pentapeptide in water: Interplay of α,α-disubstituted amino acids and the central residue on structure formation

Cα,α‐disubstituted amino acids (ααAAs) are widely used to conformationally constrain peptides. A series of pentapeptides containing dipropylglycine (Dpg) at alternating positions and their α‐amino acid counterpart L‐norvaline (Nva) analogues were synthesized to fully investigate the impact of Dpg on peptide backbone structure in aqueous solution. CD, VCD, and NMR spectral analysis suggest that Dpg containing peptides adopt more ordered structures relative to their Nva containing analogues. The central residues (Ala, Thr, Tyr, Val) and the charged side‐chains of Glu and Lys play important roles in the degree of peptide folding. Hydrophobic and branched residues (Val, Tyr) at the central position of the peptide produce greater folding as judged by CD and NMR. Variation of the chemical shift with temperature (Δδ/ΔT NH) of Ac‐Glu‐Dpg‐Tyr‐Dpg‐Lys‐NH2 suggests a series of i → i + 3 hydrogen bonds between the N‐terminal acetyl carbonyl and the Tyr3 NH, and the Glu1 carbonyl and the Dpg4 NH. The solution conformation of Ac‐Glu‐Dpg‐Tyr‐Dpg‐Lys‐NH2 calculated from NMR‐derived constraints shows a 310‐helical structure (two repetitive type‐III β‐turns) at residues 1‐4, which is supported by 2D NMR, CD, and VCD spectra. Analysis of NMR‐derived models of these peptides suggest that there is a strong hydrophobic interaction of the pro‐S propyl side chain of Dpg2 and the Tyr3 side‐chain that may be a strong stabilizing force of the peptide folding in water.

Design, Synthesis, and Conformational Studies of Short Peptides Containing C αα -Dipropylglycine and Dibenzylglycine

Non-proteinogenic Cαα-disubstituted amino acid (ααAA) residues greatly restrict the number of conformations of peptides and thus induce distinct secondary structures, even in short peptides [1]. In this work several pentapeptides containing Cαα-dipropyl-glycine (Dpg) and dibenzylglycine (Dbg) at alternating sequence positions and their L-norvaline (Nva) analogs were prepared. The design of these peptides is based on our models of amyloid β-sheet blocker peptides. Dpg and Dbg could accommodate energetically favored extended conformation [2] and thus induce the formation of β-sheet by self-aggregation.

Ethyl Nitroacetate as a Useful Synthon for the Synthesis of Orthogonally Protected, Poly-Functional C αα -Disubstituted Amino Acids

The discovery of Cα, α-disubstituted amino acids (ααAAs) and their propensity to induce secondary structure even into short peptides has resulted in an increased interest in novel methods for their synthesis [1, 2]. Herein ethyl nitroacetate, a useful synthetic intermediate for a variety of biologically significant compounds [3], has been employed for the preparation of sterically hindered and polyfunctional ααAAs which are suitable for incorporation into peptides.