4‐Naphthylmethyl Proline Forms a Channel Structure

Abstract

Proline and proline derivatives are useful tools to control the structural properties of peptides and proteins, and thereby modulate numerous processes. Here, we show that proline derivatives can have unique structural properties in the solid state by presenting the crystal structure of zwitterionic (2S,4S)/(2S,4R)‐4‐[(naphthalen‐2‐yl)methyl]proline (H‐Nap‐OH). This amphiphilic proline derivative forms a columnar structure around large hydrophilic and small hydrophobic channels with diameters of 9 Å and 4 Å, respectively. We show that this architecture, which is unprecedented for amino acids, results from the combination of a hydrogen bond network between the ammonium and carboxylate moieties and π–π as well as CH–π interactions between the aromatic moieties.

Assembly of π-Stacking Helical Peptides into a Porous and Multivariable Proteomimetic Framework

“…A coiled-coil interaction would produce two opposed pairs of bipyridyl moieties that can grow the lattice by π–π-stacking. Peptides hybridized with large aromatic moieties have been shown to reliably engage in π–π-stacking to form 1-D, 2-D, and 3-D extended assemblies. − Our design principles are culminated in the peptide sequence UIC-1 (Figure c). UIC-1 was synthesized by SPPS (Supporting Information), which provided pure compound in ∼1 day with 81% yield.…”

“…π-Stacking is a prominent structural feature of this framework that works in concert with hydrophobic and hydrogen-bonding interactions, though calculations will be needed to quantify the energetic contributions of each type of interaction. The use of π-stacking to generate porous structures is an emerging and promising noncovalent strategy. ,, The metal-free strategy is critical for tolerating useful functional groups containing carboxylic acids and N- and S-donors, which are rarely compatible with metal-coordination frameworks. Furthermore, the flexibility afforded by noncovalent assembly facilitates conformationally dynamic, proteomimetic engagement with guest molecules.…”

Pore Restructuring of Peptide Frameworks by Mutations at Distal Packing Residues

“…In this context, the pores within frameworks have structural and functional analogy to the active sites found in proteins, − which also contain precisely sized, functionalized pockets for binding or catalysis. Consequently, the utilization of peptides in the construction of framework materials holds the potential to create materials that exhibit, like proteins, remarkable complexity, specificity, and efficiency. − …”

SCS Spring Meeting 2022 on Biosupramolecular Chemistry, University of Geneva, Auditoire Marignac, April 22, 2022

“…[2,3] In her invigorating lecture, Helma Wennemers from ETH Zurich convinced the audience that they should care about collagen. [4][5][6] She showed how collagen model peptides can be chemically modified to introduce novel functionalities, for example hyperstability of the triple helix through lipidation. She concluded with exciting new work that combines a collagen peptide with a LOX activity sensor to probe and visualize areas of extensive collagen remodeling, both in vivo and in situ.…”