Turning Peptide Sequences into Ribbon Foldamers by a Straightforward Multicyclization Reaction

Abstract

The conformational control of molecular scaffolds allows the display of functional groups in defined spatial arrangement. This is of considerable interest for developing fundamental and applied systems in both the fields of biology and material sciences. Peptides afford a large diversity of functional groups, and peptide synthetic routes are very attractive and accessible. However, most short peptides do not possess well-defined secondary structures. Herein, we developed a simple strategy for converting peptide sequences into structured γ-lactam-containing oligomers while keeping the amino acids side chain diversity. We showed the propensity of these molecules to adopt ribbon-like secondary structures. The periodic distribution of the functional groups on both sides of the ribbon plane is encoded by the initial peptide sequence.

C9/12 Ribbon‐Like Structures in Hybrid Peptides Alternating α‐ and Thiazole‐Based γ‐Amino Acids

“…No chemical shift variation was observed at concentrationsf rom 1-10 mm, which suggested that no peptide self-association occurred under the analytical conditions. [19] Once again, this result supported the idea that the ribbon structure was governed by each preorganized a/(R)-ATC C 9/12 turn. Such strong NH deshielding (d > 9ppm) was formally related to formation of the typical C 9 -hydrogenb onds that surrounded the ATCresidues.…”

Incipient Twisted Ribbon Structure Stabilized by C12 Helical Turns in γ4/α Hybrid Peptide

“…The formation of C 9 ribbon structures have been investigated in the homo‐oligomers of cis‐γ‐amino‐L‐proline as well as β,β‐disubstituted‐γ‐amino acid, gabapentin (Gpn) . β‐bend ribbon conformation has been reported in α‐amino‐γ‐lactam‐based foldamers . Recently, we have reported the ribbon structure involving C 10 and C 12 intramolecular hydrogen bonds in a tetrapeptide Boc‐Pro‐Aib‐Gpn‐Pro‐NHMe .…”

Post‐Translational Backbone Engineering through Selenomethionine‐Mediated Incorporation of Freidinger Lactams

“…[1–3] Treatment with sodium hydride deprotonates the amide backbone, cyclizing to the Agl via a 5-exo-tet cyclization. [1–3] These dipeptide lactams were then utilized in solid and solution phase peptide synthesis. Since its introduction the Freidinger lactam has been incorperated into numerous biologically relevant peptide systems.…”