Straightforward solid-phase-supported synthesis routes were presented to obtain novel oligopeptide-based reversible addition fragmentation transfer (RAFT) agents. These approaches include the coupling of a functional RAFT agent to a resin-bound peptide and the functionality switch of an oligopeptide ATRP macroinitiator into an oligopeptide transfer agent. The solid-phase-supported methods allowed easy purification of the transfer agents, making difficult column purification steps unnecessary. Well-defined conjugates comprising sequence-defined peptides and synthetic polymers could be accessed by applying RAFT polymerization techniques in combination with the peptide macrotransfer agents. Polymerization reactions of n-butyl acrylate were performed in solution, yielding peptide-polymer conjugates with controllable molecular weight and low polydispersities of around 1.1. The peptide-polymer conjugates were characterized using 1 H NMR spectroscopy and size exclusion chromatography (SEC), while the incorporation of the oligopeptide into the synthetic polymer and the preservation of the chirality were shown by circular dichroism (CD) spectroscopy.

The synthesis of peptide−polymer conjugates comprising (d - alt-l)-cyclopeptides as aggregator domains and their self-assembly into tubelike structures is described. By coupling two well-defined poly(n-butyl acrylate) blocks to opposite sides of a preformed cyclic (d - alt-l)-α-octapeptide, a coil−ring−coil bioconjugate was accessed. The applied solution-phase coupling route allowed a multigram scale synthesis of the conjugate and assured both a controlled synthesis and ease of analysis. The controlled self-assembly of the conjugate leads to uniform tube structures. Atomic force microscopy (AFM) of these aggregates deposited on mica revealed a height of 1.4 ± 0.2 nm, a width of 5 nm, and roughly estimated lengths of up to 200−300 nm. A model is proposed, explaining the structure dimensions. This includes the formation of a tubular peptide core build via stacking of the cyclopeptides and a poly(n-butyl acrylate) shell wrapping around the peptide tube. The model is consistent with infrared spectroscopy and electron diffraction measurements, verifying that the peptide segment of the conjugate adopts a β-sheet structure, similar to unsubstituted (d - alt-l)-cyclopeptides. Hence, the stacks of peptide rings are stabilized along the fiber axis via inter-ring β-sheet H-bonding. The tube structures are capable to interact laterally, organizing further into weak networks as was evidenced by AFM and transmission electron microscopy.

The synthesis and self-assembly behavior of a set of peptide-polymer conjugates is described. It is demonstrated that an oligopeptide segment, composing 3.5 wt % of a conjugate, can effectively direct the microstructure formation of a poly(n-butyl acrylate)-block (pnBA) with M n ≈ 38 000. RAFT polymerization is used to synthesize conjugates possessing pnBA blocks with different block lengths (M n ) 8000-38 000) but having the same peptide-aggregator domain. The high tendency of this peptide to adopt a β-sheet is temporarily suppressed by switch and pseudoproline defects, allowing the ease of introduction of a RAFT chain-transfer moiety (CTA). The resulting peptide-CTA can effectively mediate the polymerization of n-butyl acrylate, leading to a conjugate with suppressed aggregation tendency. However, the undisturbed peptide segment is reestablished via a pH-controlled rearrangement in the defects, triggering peptide-directed microstructure formation. Atomic force microscopy (AFM) allows the visualization of fibrillar microstructures and frequently provides evidence for a left-handed superhelical fine structure. The peptide segments organize into β-sheets as proven by infrared spectroscopy (FT-IR) and electron diffraction coupled to transmission electron microscopy (SAED-TEM). Thus, peptide organization controls microstructure formation and both the dimensions of the fibrils and the approximated rates of self-assembly are correlated to the molecular weight of the pnBA blocks in the conjugates.

This article describes the synthesis and binding properties of highly selective noncovalent molecular receptors 13‚(DEB)6 and 33‚(DEB)6 for different hydroxyl functionalized anthraquinones 2. These receptors are formed by the self-assembly of three calix [4]arene dimelamine derivative molecules (1 or 3) and six diethylbarbiturate (DEB) molecules to give 13‚(DEB)6 or 33‚(DEB)6. Encapsulation of 2 occurs in a highly organized manner; that is, a noncovalent hydrogen-bonded trimer of 2 is formed within the hydrogenbonded receptors 13‚(DEB)6 and 33‚(DEB)6. Both receptors 13‚(DEB)6 and 33‚(DEB)6 change conformation from staggered to eclipsed upon complexation to afford a better fit for the 23 trimer. The receptor selectivity toward different anthraquinone derivatives 2 has been studied using 1 H NMR spectroscopy, X-ray crystallography, UV spectroscopy, and isothermal microcalorimetry (ITC). The π-π stacking between the electron-deficient center ring of the anthraquinone derivatives 2a-c and 2e-g and the relatively electronpoor melamine units of the receptor is the driving force for the encapsulation of the guest molecules. The selectivity of the hydrogen-bonded host for the anthraquinone derivatives is the result of steric interactions between the guest molecules and the calix[4]arene aromatic rings of the host.