The coiled coil is a superhelical protein structural motif that consists of two or more alpha-helical peptides that are wrapped around each other in superhelical fashion. Coiled coils are amongst the most ubiquitous folding motifs found in proteins and have not only been identified in structural proteins but also play an important role in various intracellular regulation processes as well as membrane fusion. The aim of this critical review is to highlight the potential of coiled coil peptide sequences for the development of self-assembled, responsive and/or bioactive materials. After a short historical overview outlining the discovery of this protein folding motif, the article will briefly discuss naturally occurring coiled coils. After that, the basic rules, which have been established to date for the design of coiled coils will be briefly summarized followed by a presentation of several classes of coiled coils, which may represent interesting candidates for the development of novel self-assembled, responsive and/or bioactive materials. This critical review will end with a section that summarizes the different coiled coil based (hybrid) materials that have been reported to date and which hopefully will help to stimulate further work to explore the full potential of this unique class of protein folding motifs for the development of novel self-assembled, responsive and/or bioactive materials (212 references).

β-Sheet forming self assembling cyclic peptides offer a versatile scaffold for the construction and control of hydrogen-bonded nanotube assemblies. These structures have major advantages over other nanoscale tubular structures, including sub-nanometer control over the internal diameter, and the ability to control internal and external chemical functionality. This Tutorial Review presents an overview of nanotubes derived from this class of cyclic peptides. The design rationale for functional nanotubes based on cyclic peptide ring size and chemical functionality is discussed. Additionally, we highlight the recent expansion of the nanotube toolbox through conjugation of (macro)molecules to the cyclic peptides. These provide additional functionality and control nanotube dimensions that could potentially prove beneficial in future applications.

The synthesis of multiblock copolymers is often considered as synthetically challenging and time consuming. In this contribution, the development of a remarkably efficient and versatile procedure to access multiblock copolymers via reversible addition-fragmentation chain transfer (RAFT) polymerization is reported. The robustness and versatility of the RAFT process is demonstrated in this report by preparing multiblock copolymers using uncommon experimental conditions. The synthesis of each block was performed in the presence of air and only required 3 minutes to reach >98% monomer conversion. This approach removes the necessity to deoxygenate the solution and permits access to complex copolymer structures in very short time periods. For example, this process allowed the preparation of a heptablock homopolymer with a well-defined architecture in just 21 minutes. We also discuss the limitations inherent to this approach. This strategy is shown to be particularly efficient when blocks with low degrees of polymerization (DP < 20) are targeted. For blocks with higher DPs (DP > 50), the procedure is typically limited to the preparation of di-or triblock copolymers.Functional block copolymers are fascinating architectures with unique properties that render them particularly attractive for applications ranging from medicine, 1,2 materials, 3 energy 4 and nanotechnology. 5,6 The access to such synthetically demanding architectures was greatly facilitated with the advent of controlled/"living" radical polymerization techniques, also known as reversible deactivation radical polymerization (RDRP), 7 such as atom transfer radical polymerization (ATRP), 8,9 nitroxide-mediated radical polymerization (NMP), 10,11 reversible addition-fragmentation chain transfer (RAFT) 12-15 and macromolecular design via interchange of xanthates (MADIX) 16-18 polymerizations. These methods enable the production of well-defined polymeric materials with predetermined molar masses, narrow molar mass distributions, chainend functionality, and they can be coupled with efficient post-polymerization modification strategies (e.g. 'click' chemistry). [19][20][21][22][23][24][25] Despite the relative ease of preparing block copolymers (i.e., di-or triblock copolymers) via RDRP methods in comparison with, for example, ionic living polymerizations, the production of multiblock copolymers still remains a challenging and time consuming task. This is mainly due to the necessity to remove any unreacted monomer before the subsequent block is synthesized, 26-31 as the non-removal of monomer would lead to the synthesis of quasi-block copolymers. 32Additional issues include a decrease in chain-end fidelity with increasing the number of blocks.Recently, Cu(0)-mediated radical polymerization 33-38 and RAFT polymerization 39-44 have demonstrated great potential to produce well-defined, multiblock architectures, in particular by reaching full monomer conversion, thus avoiding tedious, intermediate purification steps.

Self-assembled nanotubular structures have numerous potential applications but these are limited by a lack of control over size and functionality. Controlling these features at the molecular level may allow realization of the potential of such structures. Here we report a new generation of self-assembled cyclic peptide-polymer nanotubes with dual functionality in the form of either a Janus or mixed polymeric corona. A 'relay' synthetic strategy is used to prepare nanotubes with a demixing or mixing polymeric corona. Nanotube structure is assessed in solution using 1 H-1 H nuclear Overhauser effect spectroscopy NMR, and in bulk using differential scanning calorimetry. The Janus nanotubes form artificial pores in model phospholipid bilayers. These molecules provide a viable pathway for the development of intriguing nanotubular structures with dual functionality via a demixing or a mixing polymeric corona and may provide new avenues for the creation of synthetic transmembrane protein channel mimics.

Herein the concept of tandem postpolymerization modification as a versatile route to synthesize well-defined, highly functionalized polymers is introduced. Poly(pentafluorophenyl methacrylate) obtained by atom transfer radical polymerization was first modified with allylamine, which displaces the active ester to give well-defined polymers with pendant alkene groups, which are difficult to obtain by direct (radical) polymerization of allylic-functional monomers. The produced poly(allylmethacrylamide) was modified by a second postpolymerization modification reaction with a thiol-terminated peptide (CVPGVG) using AIBN as the radical source. NMR, IR, and SEC demonstrated successful conjugation onto the polymer to give a polymer-peptide hybrid material. This versatile strategy should extend the scope of controlled radical polymerization and "click"-type reactions.

The partition and self-assembly of a new generation of cyclic peptide-polymer conjugates into well-defined phospholipid trans-bilayer channels is presented. By varying the structural parameters of the cyclic peptide-polymer conjugates through the ligation of hydrophobic and hydrophilic polymers, both the structure of the artificial channels using large unilamellar vesicle assays and the structural parameters required for phospholipid bilayer partitioning are elucidated. In addition, temperature was used as an external stimulus for the modulation of transbilayer channel formation without requiring the redesign and synthesis of the cyclic peptide core. The thermoresponsive character of the cyclic peptide-polymer conjugates lays the foundation for on-demand control over phospholipid transmembrane transport, which could lead to viable alternatives to current transport systems that traditionally rely on endocytic pathways.

Peptides derived from the HR1 or HR2 regions of the HIV-1 envelope glycoprotein gp41 have been shown to be effective inhibitors to prevent virus−host cell membrane fusion. These peptide drugs, however, suffer from relatively short plasma half-lives and are susceptible to enzymatic degradation. Modification of peptides/proteins with poly-(ethylene glycol) (PEG) is a well-established strategy to overcome these limitations. This manuscript presents the results of a systematic study on the influence of the site of PEGylation of HR2-derived peptides, as well as of PEG molecular weight on the biological activity and proteolytic stability of these conjugates. Investigation of the fusion inhibitory efficacy of the conjugates in a model cell−cell based assay revealed a loss in activity for the PEGylated peptides as compared to the wild-type HR2-derived peptide. The loss of activity, however, can be minimized by controlling the site of PEGylation, more specifically, by introducing the PEG chain at one of the more central positions along the non-interacting αhelical surface of the peptides. The proteolytic stability of the PEG−peptide conjugates was assessed in a trypsin-based model assay, which revealed an up to 3.4-fold increase in degradation half-life that may help to compensate for the lower inhibitory efficacy of the PEG−peptide conjugates as compared to the wild-type peptide. The results of this study emphasize the power of site-specific PEGylation to improve the stability of peptide/protein drugs while minimizing adverse effects on biological activity.

This report describes the synthesis and properties of a series of polyvalent side chain peptide – synthetic polymer conjugates designed to block the CD4 binding site on gp120 and inhibit HIV-1 entry into a host cell. The peptide sequences in the conjugates are based on the CDR H3 region of the neutralizing anti-HIV-1 antibody IgG1 b12. Using a consecutive ester-amide/thiol-ene post-polymerization modification strategy, a library of polymer conjugates was prepared. Evaluation of the HIV-1 inhibitory properties revealed that mid-sized polymer conjugates displayed the highest antiviral activity, while shorter and longer conjugates proved to be less efficacious inhibitors. The lower molecular weight conjugates may not have sufficient length to span the distance between two neighboring gp120 containing spikes, while the higher molecular weight conjugates may be compromised due to a higher entropic penalty that would accompany their binding to the viral envelope. Although the IC50 values for these polymer conjugates are higher than that of the parent IgG1 b12 antibody, the strategy presented here may represent an interesting antiviral approach due to the attractive properties of such polymer therapeutics (relatively inexpensive production and purification costs, high thermal and chemical stability in storage conditions, long half life in biological tissues, low immunogenicity, protection from proteolytic degradation).