A Fiberlike Peptide Material Stabilized by Single Intermolecular Hydrogen Bonds

Abstract

One is enough: The dipeptide Boc‐L‐Phe‐D‐Oxd‐OBn (Boc=tert‐butoxycarbonyl, Phe=phenylalanine, Oxd=4‐methyl‐5‐carboxy oxazolidin‐2‐one, Bn=benzyl; see picture; gray C, white H, red O, blue N) spontaneously forms uniform fibers consisting of parallel infinite linear chains arising from single intermolecular NH⋅⋅⋅OC hydrogen bonds. This is the absolute borderline case of a parallel β‐sheet structure.

Nanofibers from Oxazolidi‐2‐one Containing Hybrid Foldamers: What is the Right Molecular Size?

“…In the dimer, only one intermolecular hydrogen bond between neighboring peptides is sufficient to form a fiber-like material with an anti-parallel b-sheet structure, thus showing that the dimer has "the right molecular size" to form nanofibers. This result is complementary to our previously published crystal structure of the blocked parent monomer Boc-l-Phe-d-Oxd-OBn, [10] which represents the borderline case for a parallel b-sheet structure with only one hydrogen bond connecting the peptide molecules.…”

“…Deprotection of the carbobenzoxy group of 3 with H 2 in methanol in the presence of Pd/C (5 %) gave the corresponding acid 4. Repetition of these steps afforded the complete foldamer series up to Boc-(l-Phe-d-Oxd) 5 -OH (10). All the deprotection steps could be performed with excellent yields.…”

“…Given that fiber formation occurred in the parent molecule Boc-l-Phe-d-Oxd-OBn, [10] we could predict that the shorter oligomers will preferentially form fibers, since competitive intramolecular hydrogen bonds are weak, or even absent. First, the oligomer series was examined by solid-state FTIR (1 % mixture in solid KBr).…”

Synthesis of Constrained Peptidomimetics Containing 2‐Oxo‐1,3‐oxazolidine‐4‐carboxylic Acids

“…The trans conformation of 2i was confirmed by comparison of the NMR spectroscopic data with that of Oxd-peptides described in the literature. [11,12] In Oxd-peptides, the carbonyl group of the cycle introduces a constraint that forces the pseudo-peptide bond to always have the trans conformation. This feature should be of help to investigate the bioactive conformation of EM1, which is an aspect that is under investigation.…”

“…[12] The synthesis of the oxazolidin-2-one ring from an amino alcohol and a carbonate or a dicarbonate (CDI, diethyl or diphenyl carbonate, Boc 2 O, etc.) is well documented.…”