5 research outputs found
Foldamers of β-peptides : conformational preference of peptides formed by rigid building blocks : The first MI-IR spectra of a triamide nanosystem
To determine local chirality driven conformational preferences of small aminocyclobutane-1-carboxylic acid derivatives, X-(ACBA) n -Y, their matrix-isolation IR spectra were recorded and analyzed. For the very first time model systems of this kind were deposited in a frozen (~10 K) noble gas matrix to reduce line width and thus, the recorded sharp vibrational lines were analyzed in details. For cis-(S,R)-1 monomer two “zigzag” conformers composed of either a six or an eight-membered H-bonded pseudo ring was identified. For trans-(S,S)-2 stereoisomer a zigzag of an eight-membered pseudo ring and a helical building unit were determined. Both findings are fully consistent with our computational results, even though the relative conformational ratios were found to vary with respect to measurements. For the dimers (S,R,S,S)-3 and (S,S,S,R)-4 as many as four different cis,trans and three different trans,cis conformers were localized in their matrix-isolation IR (MI-IR) spectra. These foldamers not only agree with the previous computational and NMR results, but also unambiguously show for the first time the presence of a structure made of a cis,trans conformer which links a “zigzag” and a helical foldamer via a bifurcated H-bond. The present work underlines the importance of MI-IR spectroscopy, applied for the first time for triamides to analyze the conformational pool of small biomolecules. We have shown that the local chirality of a β-amino acid can fully control its backbone folding preferences. Unlike proteogenic α-peptides, β- and especially (ACBA) n type oligopeptides could thus be used to rationally design and influence foldamer’s structural preferences
Secondary Structure of Short β‑Peptides as the Chiral Expression of Monomeric Building Units: A Rational and Predictive Model
Chirality of the monomeric residues controls and determines
the
prevalent folding of small oligopeptides (from di- to tetramers) composed
of 2-aminocyclobutane-1-carboxylic acid (ACBA) derivatives with the
same or different absolute and relative configuration. The <i>cis</i>-form of the monomeric ACBA gives rise to two conformers,
namely, Z6 and Z8, while the <i>trans</i>-form manifests
uniquely as an H8 structure. By combining these subunits in oligo-
and polypeptides, their local structural preference remains, thus
allowing the rational design of new short foldamers. A lego-type molecular
architecture evolves; the overall look depends only on the conformational
properties of the structural building units. A versatile and efficient
method to predict the backbone folds of designed cyclobutane β-peptides
is based on QM calculations. Predictions are corroborated by high-resolution
NMR studies on selected stereoisomers, most of them being new foldamers
that have been synthesized and characterized for the first time. Thus,
the chiral expression of monomeric building units results in the defined
secondary structures of small oligomers. As a result of this study,
a new set of chirality controlled foldamers is provided to probe as
biocompatible biopolymers