1,2,3‐Triazole Bridge as Conformational Constrain in β‐Hairpin Peptides: Analysis of Hydrogen‐Bonded Positions

Abstract

Conformational constrained β-hairpin peptides are useful tool to modulate protein-protein interactions. A triazole bridge in hydrogen-bonded positions between two antiparallel strands induces a conformational stabilization of the β-hairpin peptide. The entity of the stability of the β-hairpin peptide depends on the length of the bridge.

Design and structural characterisation of monomeric water-soluble α-helix and β-hairpin peptides: State-of-the-art

“…It has been found that, when a Trp/Trp interaction in a non-HB is replaced by a triazol-bridge, β-hairpin stability depends on the length of the triazole-linker [268]. The stabilising effect of triazol-bridges at HB positions also depends on the length of the triazole-linker [269].…”

Computational Evolution of Threonine-Rich β-Hairpin Peptides Mimicking Specificity and Affinity of Antibodies

“…The lack of the expected loss of 26 Da due to reduction of azide to amine showed that no unreacted azide was left. 51 The bridged β-bodies 8 and 9 retained their ability to bind to GFP and IL-1β, as shown in Figure 6B.…”

“…Relying on our long-standing experience 8,37 with the Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction, 52−54 two Thr residues on opposite strands of the same β-body were substituted with propargyl glycine (Pra) and γ-azido-α-aminobutyric acid (Dab-N 3 ), respectively. 8,51 Using CuBr as catalyst, triazole bridge formation was quantitatively induced. Intramolecular cyclization was confirmed to have taken place by treating the product with DTT followed by mass spectrometric analysis (see Figures S20 and S21).…”

Macrocyclization strategies for cyclic peptides and peptidomimetics

“…264 When a short spacer on the C-terminus is desired for headto-tail cyclization, it is possible to introduce a C-terminal propargylamine by using a silyl-based alkyne modifying (SAM)-resin. 272,273 CuAAC does not require protecting groups and can be performed on-resin 267,271,[274][275][276][277][278] as well as in solution, 262,[265][266][267][268][269][279][280][281][282][283][284][285][286][287][288][289][290][291][292][293][294][295] which is more common and proceeds under mild conditions. Cu salts most frequently used are CuSO 4 with sodium ascorbate, or Cu I salts such as CuI and…”