Synthesis and Conformational Characterisation of Hexameric β‐Peptide Foldamers by Using Double POAC Spin Labelling and cw‐EPR

Abstract

A selected set of terminally protected β-hexapeptides, each containing two nitroxide-based (3R,4R)-4-amino-1-oxyl-2,2,5,5-tetramethylpyrrolidine-3-carboxylic acid (POAC) residues combined with four (1S,2S)-2-aminocyclopentane-1-carboxylic acid (ACPC) residues, was synthesised by using solution methods and was fully characterised. The two POAC residues are separated in the sequences by different numbers of intervening ACPC residues. The conformational features of the doubly spin-labelled β-hexapeptides were examined in chloroform by FTIR absorption and continuous-wave electron paramagnetic resonance spectroscopic techniques. In particular, the biradical exchange coupling (J) between two POAC residues within each peptide indicates unambiguously that the secondary structure overwhelmingly adopted is the 12-helix. Taken together, these results support the view that POAC is an excellent β-amino acid for exploring this type of helical conformation in doubly labelled β-peptides.

Membrane active Janus-oligomers of β3-peptides

“…FTIR spectroscopy can be used for characterization of β-peptide sequences. 70 , 71 Similarly, to IR spectra of natural proteins and peptides, the amide I and II absorption bands, originating mainly from C O stretching and N–H bending vibrations (∼1651 and ∼1540 cm –1 ) of the peptide backbone were considered. 72 – 74 The amide I vibration depends on the backbone structure and is commonly used for secondary structure analysis by fitting with components bands or by decomposing into basis spectra.…”

The spin label amino acid TOAC and its uses in studies of peptides: chemical, physicochemical, spectroscopic, and conformational aspects

“…Studies of POAC, as well as of β-TOAC, have addressed synthesis, separation, identification, spectroscopic characterization, and absolute configuration assignment of pure enantiomers (Wright et al 2003a, b, 2005, 2008; Péter et al 2003; Dutot et al 2008). The synthesis and conformational characterization of hexapeptides double-labeled with β-TOAC and POAC have also been reported (Wright et al 2007, 2010). Figure 2 presents the structures of the nitroxide-containing α- and β-amino acids TOAC, POAC, and β-TOAC, as well as of the C α,α -disubstituted glycines Aib and Ac6c.…”

Polyhydroxylated Cyclopentane β-Amino Acids Derived from d-Mannose and d-Galactose: Synthesis and Protocol for Incorporation into Peptides

“…So, starting from carboxylic acid 18c , esterification with trimethylsilylethanol provided the expected cyclopentenecarboxylic acid ester 18e , which furnished β-amino acid derivative 19f when subjected to the aza-Michael addition using benzylamine as the nucleophile. Hydrolysis of this ester 19f under mild basic conditions with TBAF resulted in carboxylic acid 19g , which was efficiently transformed into tripeptide 23a by direct coupling with dipeptide 22a . Removal of the N -benzyl-protecting group of 23a , by catalytic hydrogenation, provided its free amino derivative 23b , which gave pentapeptide 24 when reacted with dipeptide 22b under the stated coupling conditions.…”