The synthesis of multisegmented polymers containing repetitive oligo-( Bn Asp n , Bn Glu n ) sequences separated by methylene units and their secondary structure formation in solution and in the solid state are reported. The oligo-amino acids act as dynamic folding elements, introducing conformational changes within these multisegmented polymers depending on their nature, chain length, and temperature in either hexafluoroisopropanol (HFIP) solution or in the solid state. Combining ring-opening polymerization (ROP) of N-carboxyanhydrides with postfunctionalization of the respective N-terminus yields the oligo-( Bn Asp 3 , Bn Asp 10 , Bn Glu 3 , and Bn Glu 10 ) sequences bearing terminal vinyl groups on either side of the polymer chain. Subsequent acyclic diene metathesis (ADMET) polymerization and fractionation by preparative gel permeation chromatography generate polymers of a precise degree of polymerization (n = 3, 10; m = 1−136), allowing to investigate chain length-dependent secondary structure formation of the oligo-( Bn Asp n , Bn Glu n ) sequences. Polymers bearing Bn Asp n -esters as the repeating element show a transition from α-helices to β-sheets in HFIP solution, as proven by Fourier transform infrared and circular dichroism spectroscopic investigations, whereas Bn Glu n esters in the solid state stabilize preferably into β-sheets with increasing chain length and temperature. As a consequence, β-sheet conformation is identified as the thermodynamically more stable conformation, as supported by our experiments in the solid state and in solution.
The secondary structure of poly(amino acids) is an excellent tool for controlling and understanding the functionality and properties of proteins. In this perspective article the secondary structures of the homopolymers of oligo‐ and poly‐glutamic acid (Glu), aspartic acid (Asp), and α‐aminoisobutyric acid (Aib) are discussed. Information on external and internal factors, such as the nature of side groups, interactions with solvents and interactions between chains is reviewed. A special focus is directed on the folding in hybrid‐polymers consisting of oligo(amino acids) and synthetic polymers. Being part of the SFB TRR 102 “Polymers under multiple constraints: restricted and controlled molecular order and mobility” this overview is embedded into the cross section of protein fibrillation and supramolecular polymers. As polymer‐ and amino acid folding is an important step for the utilization and design of future biomolecules these principles guide to a deeper understanding of amyloid fibrillation.
2-Aminoisobutyric acid (Aib) is an essential amino acid, leading to the formation of peptAibols as microbiologically active peptides and proteins. We here report on the ring-opening polymerization (ROP) of Aib-NCA (N-carboxy-anhydrides), enabling to prepare distinct Aib-polymers up to molecular weights of 1400 g/mol with precise end-group control. ROP of Aib-NCA was accomplished via various amine initiators in frozen and liquid solvent systems, in all cases revealing the desired structures as detected by MALDI-TOF-MS and 1 H NMR. We can prove living polymerization behavior until the limit of solubility via inline-IR spectroscopy in both solution and solid state polymerization, characterizing the final polymers via MALDI-TOF-analysis. The attachment of chiral (D or L)-amino acids onto the polymer' headgroup allows to systematically investigate the helical screw-sense of poly(Aib) n , resulting in chiral induction to form either left (M)-or right (P)-handed screw-senses, depending on the chirality of the attached amino acid. The approach is extended toward a switchable, chiral azo-headgroup, able to change chirality of the attached poly(Aib) n via a light-induced trigger, revealing a thermally stable cis-isomer when polymer units are attached. In contrast to many other amino acids easily polymerized into poly(amino-acids) via ring-opening polymerization (ROP) of their respective Ncarboxyanhydrides (NCAs), the ROP of Aib-NCA (N-carboxy-anhydrides) here is novel and opens a general approach toward chiral, end group-modified helices with a defined screw-sense.
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