Bispidine as a helix inducing scaffold: examples of helically folded linear peptides

Abstract

We designed and synthesized bispidine-anchored peptides and showed that these peptides as small as (containing four chiral α-amino acid residues) adopt a right handed helical conformation. Bispidine anchored linear peptide adopts a helical conformation in solution and in the solid state.

Bispidine as a β-strand nucleator: from a β-arch to self-assembled cages and vesicles

“…Bispidine peptide conjugate adopts conformation based on the nature of the linkage between peptide and scaffold. 20,21 The bispidine was incorporated into the peptide by a typical peptide coupling procedure (Scheme S1 †). A series of bispidine-peptide conjugates with an increasing number of amino acids were designed and synthesized (Fig.…”

“…19 Bispidine serves as a versatile scaffold for nucleating secondary structures such as reverse turn, helix, and sheet in peptides. 20,21 The nature of the linkage between the peptide fragments and the bispidine scaffold is crucial for nucleating specific secondary structures. Here we show that the bispidine could nucleate isolated β-strand and βarch super secondary structures along with their intrinsic ability to self-assemble.…”

Modulation of prion polymerization and toxicity by rationally designed peptidomimetics

“…The molecular architecture of conjugated hydrophobic/aromatic residues could modulate and control the complex process of PrP C → PrP Sc conversion. We hypothesized that the bicyclic rigid bispidine unit (3,7-diazabicyclo [3.3.1] nonane) with two nitrogen atoms at ∼2.8 Å is ideal to append amino acids for interfering with protein-protein interactions [56]. Bispidine is a versatile secondary structure nucleator [57].…”

Split‐Ugi Reaction with Chiral Compounds: Synthesis of Piperazine‐ and Bispidine‐Based Peptidomimetics

“…PPIs determine the biological role of the relative proteins, and only in the last decade have begun to gain attention as viable targets for therapeutic intervention . Only a few studies have been published on the application of diamine‐based conformationally constrained peptidomimetics for regulating PPIs . We believe that such a unexplored class of potential PPI modulators is virtually accessible via the split‐ Ugi reaction in a straightforward manner.…”

“…Indeed, when both N‐atoms of the bispidine core are alkylated, an open‐turn is observed, while when both N‐atoms are acylated, a β ‐sheet conformation is induced. A helical conformation can be obtained if one N‐atom is alkylated and the other one acylated . Helix is one of the most common peptide secondary structures and a major recognition motif of PPIs, currently a compelling therapeutic target for small molecules‐based drug discovery .…”