Oligopeptides stand out for their remarkable structural variability, ease of synthesis, and amenability to functionalization, making them exceedingly appealing for crafting functional nanostructured materials. The low metabolic stability of natural peptides can be overcome by replacing α-amino acids with β3- amino acids, to yield artificial peptides best described as substituted β3-oligoamides. Controlling the morphology of such structures by varying the amino acid residues and altering the oligoamide termini makes it possible to adapt the core design to a range of hierarchical structures and function. Conductivity is a desired property in such nanomaterials; preferably conductive materials should be chemically anchored to a highly conductive metal, such as gold surface to connect to macroscopic electronics. It is preferable to use thiol functionality, however β3 cysteine is not synthetically achieveable. In this study β3 [SLIA] oligoamide has been synthesized and functionalized at the N terminus with a thiol moiety. After successful synthesis and purification, the thiolated oligoamide was physically characterized to confirm binding to gold, self-assembly and hetero assembly on these anchor points. It was demonstrated with a quartz crystal microbalance (QCM) that self-assembling monolayers can be formed on a gold surface and the formation of a S-Au bond was confirmed with X-ray photoelectron spectroscopy. Growth of Ac-β3[WKLWEL] fibres on these anchor points was confirmed by using atomic force microscopy and QCM. Hence, a viable metal anchor has been established that lays the foundations for the future development of molecular electronics based on β3 oligoamides.

Substituted oligoamides are short sequences of unnatural amino acids. Oligoamides made entirely of beta(3) amino acids yield helical monomers that, if N-acylated, assemble into nanorod structures via a supramolecular assembly motif. In this work, coordination crosslinking was used to create complex nanomaterials from oligoamides WKLWEL (KE) and WELWEL (EE) (the letters denote the analogous alpha-amino acids). Upon Cu(II) addition, atomic force microscopy and small angle neutron scattering revealed morphologic changes specific to KE but absent in EE. Vibration spectroscopy measurements revealed that Cu(II) can coordinate to the amine moieties of the side chains, without direct effect on the backbone amides. While coordination in excess solvent lead to regular nanostructures, fast drying of the sample yielded oligoamide templated crystallization of CuCl2. The metal coordination crosslinking of supramolecular assemblies as reported here is the first realization of a metallosupramolecular framework structure. [GRAPHICS] .

Correction for ‘A two-dimensional metallosupramolecular framework design based on coordination crosslinking of helical oligoamide nanorods’ by Norton G. West et al., Mater. Adv., 2020, 1, 1134–1141, DOI: 10.1039/D0MA00123F.

Coordination crosslinking of oligoamide nanorods yields two dimensional metallosupramolecular framework.

Purpose Drug-eluting balloon catheters (DEBc) coated with paclitaxel (PTX) have been associated with potential safety concerns. An efficacious but less toxic balloon coating may reduce these outcomes. We evaluated a novel DEBc, Epi-Solve, coated with metacept-3 (MCT-3), a member of the histone deacetylase inhibitor (HDACi) class of epigenetic agents, in a large animal model of neointimal hyperplasia (NIH). Methods Plain balloon angioplasty (PABA) catheters were ultrasonically coated with MCT-3 to generate Epi-Solve DEBc. An ovine model of NIH formation was established utilising partial left common carotid artery (LCA) ligation. Twenty-eight days post neointima (NI) induction, PABA, Epi-Solve or PTX-coated DEBc were deployed at the site of induced NI formation. Twenty-eight days post-intervention, ligated vessels were evaluated for attenuation of NI formation, gene expression profiles and immunohistochemical analysis. Results Epi-Solve DEBc demonstrated attenuation of NIH over no intervention and a trend to inhibition of NIH over PABA. Gene expression analysis and immunohistochemical studies identified significant anti-proliferative and anti-inflammatory signatures and reduced vascular endothelial cell activation compared to PABA. Conclusions Epi-Solve is a novel HDACi-coated DEBc which demonstrates significant anti-proliferative and anti-inflammatory signatures and reduced vascular endothelial cell activation compared to PABA in an ovine model and may afford endothelial protection.

Peptides comprised entirely of β3-amino acids, commonly referred to as β-foldamers, have been shown to self-assemble into a range of materials. Previously, β-foldamers have been functionalised via various side chain chemistries to introduce function to these materials without perturbation of the self-assembly motif. Here, we show that insertion of both rigid and flexible molecules into the backbone structure of the β-foldamer did not disturb the self-assembly, provided that the molecule is positioned between two β3-tripeptides. These hybrid β3-peptide flanked molecules self-assembled into a range of structures. α-Arginlyglycylaspartic acid (RGD), a commonly used cell attachment motif derived from fibronectin in the extracellular matrix, was incorporated into the peptide sequence in order to form a biomimetic scaffold that would support neuronal cell growth. The RGD-containing sequence formed the desired mesh-like scaffold but did not encourage neuronal growth, possibly due to over-stimulation with RGD. Mixing the RGD peptide with a β-foldamer without the RGD sequence produced a well-defined scaffold that successfully encouraged the growth of neurons and enabled neuronal electrical functionality. These results indicate that β3-tripeptides can form distinct self-assembly units separated by a linker and can form fibrous assemblies. The linkers within the peptide sequence can be composed of a bioactive α-peptide and tuned to provide a biocompatible scaffold.

In this work, we demonstrate the potential of surface-initiated single electron transfer living radical polymerization for surface modification applications that confer low-fouling properties. The versatility of the technique, which can be applied to a wide variety of substrates, has been displayed by the successful grafting of a range of monomers after immobilizing a bromine initiator on the surface via plasma polymerization. The thickness of the grafted surfaces can be controlled through variation of reaction parameters such as monomer concentration, reaction time, and the ratio between catalyst and ligand. Furthermore, the low-fouling properties of the resulting surfaces were demonstrated against fully concentrated serum proteins and adhesive fibroblast cells, via grafting of N-hydroxyethyl acrylamide (N-HEA) or [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide (SBMA). This rapid and versatile coating technique, which has the ability to be applied to a wide range of substrates, can be performed in aqueous conditions without the exclusion of atmospheric oxygen, and shows excellent potential for the surface modification of biomaterial surfaces that require low-fouling properties. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017

Abstract Unnatural peptide self-assembly offers the means to design hierarchical nanostructures of controlled geometries, chemical function and physical properties. N-acyl β3 peptides, where all residues are unnatural amino acids, are able to form helical fibrous structures by a head-to-tail assembly of helical monomers, extending the helix via a three point supramolecular hydrogen bonding motif. These helical nanorods were shown to be stable under a wide range of physical conditions, offering a self-assembled analogue of polymeric fibres. Hitherto the self-assembly has only been demonstrated between identical monomers; however the self-assembly motif is sequence-independent, offering the possibility of hetero-assembly of different peptide monomers. Here we present a proof of principle study of head-to-tail co-assembly of two different helical unnatural peptides Ac-β3[WELWEL] and Ac-β3[LIA], where the letters denote the β3 analogues of natural amino acids. By atomic force microscopy imaging it was demonstrated that the homo-assembly and co-assembly of these peptides yield characteristically different structures. Synchrotron small angle X-ray scattering experiments have confirmed the presence of the fibres in the solution and the averaged diameters from modelled data correlate well to the results of AFM imaging. Hence, there is evidence of co-assembly of the fibrous superstructures; given that different monomers may be used to introduce variations into chemical and physical properties, the results demonstrate a self-assembled analogue of a statistical co-polymer that can be used in designing complex functional nanomaterials.

Grb7 is a signaling protein with critical roles in tumor cell proliferation and migration and an established cancer therapeutic target. Here we explore chemical space to develop a new bicyclic peptide inhibitor, incorporating thioether and lactam linkers that binds with affinity (KD = 1.1 μM) and specificity to the Grb7-SH2 domain. Structural analysis of the Grb7-SH2/peptide complex revealed an unexpected binding orientation underlying the binding selectivity by this new scaffold. We further incorporated carboxymethylphenylalanine and carboxyphenylalanine phosphotyrosine mimetics and arrived at an optimized inhibitor that potently binds Grb7-SH2 (KD = 0.13 μM) under physiological conditions. X-ray crystal structures of these Grb7-SH2/peptide complexes reveal the structural basis for the most potent and specific inhibitors of Grb7 developed to date. Finally, we demonstrate that cell permeable versions of these peptides successfully block Grb7 mediated interactions in a breast cancer cell line, establishing the potential of these peptides in the development of novel therapeutics targeted to Grb7.

Chromatography with mass spectrometry (MS) is a technique of choice for metabolomic analysis of plant extracts. Single dimension gas chromatography (1DGC) with MS leads to poorly resolved metabolites of complex Eucalyptus spp. leaf oil secondary metabolites and consequently limited metabolic coverage of secondary compounds. Multidimensional chromatography with high resolution MS can contribute to advances in this field.

We have described a new class of hydrogelator based on helical β(3)-peptides carrying a bioactive payload. The β(3)-peptides self-assemble in aqueous solution to form a nanofibrous mesh resulting in a stable hydrogel. The simple design provides the versatility for attaching different functional payloads to the β(3)-peptide scaffold to develop new materials.

Event Abstract Back to Event Ultra-short self-assembled beta-peptide hydrogels as matrices for neural tissue engineering Sepideh Motamed1*, Mark Del Borgo2*, Ketav Kulkarni3*, Nathan Habila2, Kun Zhou1, David Finkelstein4, Patrick Perlmutter3*, Marie I. Aguilar2 and John S. Forsythe1* 1 Monash University, Department of Materials Science and Engineering, Australia 2 Monash University, Department of Biochemistry and Molecular Biology, Australia 3 Monash University, School of Chemistry, Australia 4 The University of Melbourne, Florey Department of Neuroscience and Mental Health, Australia Hydrogels have physical features of soft tissue and have been explored for their use in nerve regeneration and drug delivery [1]. Hydrogels based on peptide self-assembly are extremely promising candidates to provide a suitable microenvironment for cells due to their facile synthesis, simple building blocks, inherent biocompatibility and the ability to control the structural and functional properties of the end product [2]-[4]. However, applying the peptide hydrogel matrices in brain tissue engineering is faced with a number of key challenges. Peptide-based biomaterials that are used in neural tissue engineering have been based on α-amino acid peptides which can undergo rapid proteolysis and are unable to provide long term structural support. In cases where the matrix must fill and provide structural support in a large brain lesion, it may be preferable to use a non-degrading or permanent peptide matrix [5]. Herein we introduce for the first time hydrogels consisting of peptide matrix composed of only β3-amino acids as an efficient alternative for neural tissue engineering and to utilise their inherent proteolytic stability in vivo [6]. To provide the required conditions for self-assembly the N-terminus of β-tripeptide (AzKA) was capped with an acetyl group which produced a total of six axially oriented hydrogen bonding interactions [7]. A hydrophobic alkyl chain was added laterally to the peptide backbone to ensure the formation of stable hydrogel. Peptide self-assembled spontaneously to form a hydrogel upon dissolving in PBS buffer (pH 7.4) under physiological conditions at a concentration of 10mg/mL. The morphology of the formed nanofibers was further investigated by AFM and TEM which revealed a network of nanofibers with consistent diameter. The mechanical properties of the peptide hydrogel were tested via rheological studies. The hydrogel showed viscoelastic properties with storage modulus in the range of 1kPa. A balance between hydrophilic and hydrophobic domain in the peptide, allowed the hydrogel to flow under applied shear strain and to recover completely within seconds upon relaxation. To check the feasibility of the hydrogel for neural tissue engineering, the viability of SN4741, substantia nigra dopaminergic neuronal progenitor cell line, cultured on the hydrogel were assayed. The hydrogel proved to be highly biocompatible and even though it did not possess any bioactive motif, by pre-depositing protein from serum, it provided an environment for cells to adhere and proliferate with 80% cell viability in comparison to the positive control (cultured on TCPS). The facile design and synthesis of a β-peptide hydrogel can thus allow formation of controlled and variable biomaterials for different types of tissue engineering applications. References:[1] D. R. Nisbet, K. E. Crompton, M. K. Horne, D. I. Finkelstein and J. S. Forsythe, "Neural tissue engineering of the CNS using hydrogels," Journal of Biomedical Materials Research Part B: Applied Biomaterials. Vol. 87B, Oct. 2008.[2] R. G. Ellis-Behnke, Y.-X. Liang, S.-W. You, D. K. C. Tay, S. Zhang, K.-F. So and G. E. Schneider, "Nano neuro knitting: Peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision," Proceedings of the National Academy of Sciences of the United States of America. Vol. 103, March 2006.[3] M. Zhou, A. M. Smith, A. K. Das, N. W. Hodson, R. F. Collins, R. V. Ulijn and J. E. Gough, "Self-assembled peptide-based hydrogels as scaffolds for anchorage-dependent cells," Biomaterials. Vol. 30, May 2009.[4] E. J. Berns, S. Sur, L. Pan, J. E. Goldberger, S. Suresh, S. Zhang, J. A. Kessler and S. I. Stupp, "Aligned neurite outgrowth and directed cell migration in self-assembled monodomain gels," Biomaterials. Vol. 35, Jan. 2014.[5] S. Woerly, P. Petrov, E. Sykova, T. Roitbak, Z. Simonova and A. R. Harvey, "Neural tissue formation within porous hydrogels implanted in brain and spinal cord lesions: ultrastructural, immunohistochemical, and diffusion studies," Tissue Eng. Vol. 5, Oct. 1999.[6] R. P. Cheng, S. H. Gellman and W. F. DeGrado, "beta-Peptides: from structure to function," Chem Rev. Vol. 101, Oct. 2001.[7] M. P. Del Borgo, A. I. Mechler, D. Traore, C. Forsyth, J. A. Wilce, M. C. J. Wilce, M.-I. Aguilar and P. Perlmutter, "Supramolecular Self-Assembly of N-Acetyl-Capped β-Peptides Leads to Nano- to Macroscale Fiber Formation," Angewandte Chemie International Edition. Vol. 52, Aug. 2013. Keywords: Hydrogel, in vitro, Scaffold, mechanical property Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Synthetic scaffolds as extracellular matrices Citation: Motamed S, Del Borgo M, Kulkarni K, Habila N, Zhou K, Finkelstein D, Perlmutter P, Aguilar MI and Forsythe JS (2016). Ultra-short self-assembled beta-peptide hydrogels as matrices for neural tissue engineering. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.01549 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. * Correspondence: Dr. Sepideh Motamed, Monash University, Department of Materials Science and Engineering, Melbourne, Australia, Email1 Dr. Mark Del Borgo, Monash University, Department of Biochemistry and Molecular Biology, Melbourne, Australia, Mark.DelBorgo@monash.edu Dr. Ketav Kulkarni, Monash University, School of Chemistry, Melbourne, Australia, ketav.kulkarni@monash.edu Dr. Patrick Perlmutter, Monash University, School of Chemistry, Melbourne, Australia, Patrick.Perlmutter@monash.edu Dr. John S Forsythe, Monash University, Department of Materials Science and Engineering, Melbourne, Australia, John.Forsythe@monash.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Sepideh Motamed Mark Del Borgo Ketav Kulkarni Nathan Habila Kun Zhou David Finkelstein Patrick Perlmutter Marie I Aguilar John S Forsythe Google Sepideh Motamed Mark Del Borgo Ketav Kulkarni Nathan Habila Kun Zhou David Finkelstein Patrick Perlmutter Marie I Aguilar John S Forsythe Google Scholar Sepideh Motamed Mark Del Borgo Ketav Kulkarni Nathan Habila Kun Zhou David Finkelstein Patrick Perlmutter Marie I Aguilar John S Forsythe PubMed Sepideh Motamed Mark Del Borgo Ketav Kulkarni Nathan Habila Kun Zhou David Finkelstein Patrick Perlmutter Marie I Aguilar John S Forsythe Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

We report a new class of β-peptide based hydrogel for neural tissue engineering. Our β-peptide forms a network of nanofibres in aqueous solution, resulting in a stable hydrogel at physiological conditions. The hydrogel shows excellent compatibility with neural cells and provides a suitable environment for cells to adhere and proliferate.

β(3)-amino acid based polypeptides offer a unique starting material for the design of self-assembled nanostructures such as fibres and hierarchical dendritic assemblies, due to their well-defined helical geometry in which the peptide side chains align at 120° due to the 3.0-3.1 residue pitch of the helix. In a previous work we have described the head-to-tail self-assembly of N-terminal acetylated β(3)-peptides into infinite helical nanorods that was achieved by designing a bioinspired supramolecular self-assembly motif. Here we describe the effect of consecutively more polar side chains on the self-assembly characteristics of β(3)-tetrapeptides Ac-β (3)Ala-β(3)Leu-β(3)Ile-β(3)Ala (Ac-β(3)[ALIA]), Ac-β(3)Ser-β(3)Leu-β(3)Ile-β(3)Ala (Ac-β(3)[SLIA]) and Ac-β (3)Lys-β (3)Leu-β(3)Ile-β (3)Glu (Ac-β(3)[KLIE]). β(3)-tetrapeptides complete 1 1/3 turns of the helix: thus in the oligomeric form the side chain positions shift 120° with each added monomer, forming a regular periodic pattern along the nanorod. Dynamic light scattering (DLS) measurements confirmed that these peptides self-assemble even in highly polar solvents such as water and DMSO, while diffusion-ordered NMR spectroscopy revealed the presence of a substantial monomeric population. Temperature dependence of the size distribution in DLS measurements suggests a dynamic equilibrium between monomers and oligomers. Solution casting produced distinct fibrillar deposits after evaporating the solvent. In the case of the apolar Ac-β(3)[ALIA] the longitudinal helix morphology gives rise to geometrically defined (∼70°) junctions between fibres, forming a mesh that opens up possibilities for applications e.g. in tissue scaffolding. The deposits of polar Ac-β(3)[SLIA] and Ac-β(3)[KLIE] exhibit fibres in regular parallel alignment over surface areas in the order of 10 μm.

The design of potent and specific peptide inhibitors to therapeutic targets is of enormous utility for both proof-of-concept studies and for the development of potential new therapeutics. Grb7 is a key signaling molecule in the progression of HER2 positive and triple negative breast cancers. Here we report the crystal structure of a stapled bicyclic peptide inhibitor G7-B1 in complex with the Grb7-SH2 domain. This revealed an unexpected binding mode of the peptide, in which the staple forms an alternative contact with the surface of the target protein. Based on this structural information, we designed a new series of bicyclic G7 peptides that progressively constrain the starting peptide, to arrive at the G7-B4 peptide that binds with an approximately 2-fold enhanced affinity to the Grb7-SH2 domain ( K D = 0.83 μM) compared to G7-B1 and shows low affinity binding to Grb2-, Grb10- and Grb14-SH2 domains ( K D > 100 μM). Furthermore, we determined the structure of the G7-B4 bicyclic peptide in complex with the Grb7-SH2 domain, both before and after ring closing metathesis to show that the closed staple is essential to the target interaction. The G7-B4 peptide represents an advance in the development of Grb7 inhibitors and is a classical example of structure aided inhibitor development.

Event Abstract Back to Event Photo-triggered release of an antibiotic from an in situ forming hydrogel for antibacterial wound dressings Yue Shi1, Vinh X. Truong1, Ketav Kulkarni2, Yue Qu3, George P. Simon1, Richard L. Boyd4, Patrick Perlmutter2, Trevor Lithgow3 and John S. Forsythe1 1 Monash institute of Medical Engineering, Monash University, Department of Material Science and Engineering, Australia 2 Monash University, Department of Chemistry, Australia 3 Monash University, Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiolog, Australia 4 Monash University, Faculty of Medicine, Nursing and Health Sciences Anatomy and Developmental Biology, Australia Introduction: Hydrogels have been used as advanced wound dressing materials because of their ability to improve healing rates and wound appearance[1],[2]. Bacterial infections are found to be a prevalent and persistent problem during chronic wound healing and therefore antimicrobial dressings that are able to release of antibiotics using an external trigger are highly advantageous as sustained release is suspected of causing bacterial resistance[3],[4]. Using light as a trigger is of a considerable interest due to its non- invasive stimulation[5]. Herein, we present a newly designed antimicrobial hydrogel for ‘spray on’ wound dressing applications in which the timing and amount of antibiotic release can be controlled by UV light. Methodology: A representative antibiotic ciprofloxacin was chemically modified and covalently attached on a clickable PEG hydrogel network through a nitrobenzyl carbamate photolabile group. Both the hydrogel network formation and antibiotic attachment were based on a bio-orthogonal catalyst free strain promoted alkyne-zaide cycloaddition (SPAAC). Characterizations were carried out on the hydrogel mechanical properties and drug release properties. Results and discussion: With antibiotic loaded, the hydrogel maintained good mechanical properties and gelation time making it suitable as a ‘spray on’ wound dressing. NMR results indicated the cleavage of carbamate linkage occurred due to UV irradiation. Both HPLC and bacterial tests further confirmed that the native antibiotic could be cleaved from the hydrogel network using a light stimulus and diffuse into the surrounding environment inhibiting bacteria growth efficiently. The amount of drug released was quantitatively measured by HPLC and that the UV light not only triggered the release but also control the amount by different UV dosage as well. Conclusion: Together with the relative fast gelation time, the results suggest using the photo responsive strategy to deliver antibiotics provides control over the timing and dose making it potentially suitable for external wound dressing applications. References:[1] F. Han, Y. Dong, A. Song, R. Yin and S. Li, "Alginate/chitosan based bi-layer composite membrane as potential sustained-release wound dressing containing ciprofloxacin hydrochloride."Applied Surface Science, 2014, 311, 626-634.[2] L. G. Ovington, "Advances in wound dressings." Clinics in Dermatology, 2007, 25, 33-38.[3] K. Vasilev†, J. Cook and H. J. Griesser, "Antibacterial surfaces for biomedical devices." Expert Review of Medical Devices, 2009, 6, 553-567.[4] A. M. Kloxin, A. M. Kasko, C. N. Salinas and K. S. Anseth, "Photodegradable Hydrogels for Dynamic Tuning of Physical and Chemical Properties. " Science, 2009, 324, 59-63. Keywords: Infection, Light, Drug delivery, Bioactive molecule Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Biomaterials in wound healing Citation: Shi Y, Truong VX, Kulkarni K, Qu Y, Simon GP, Boyd RL, Perlmutter P, Lithgow T and Forsythe JS (2016). Photo-triggered release of an antibiotic from an in situ forming hydrogel for antibacterial wound dressings. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02181 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Yue Shi Vinh X Truong Ketav Kulkarni Yue Qu George P Simon Richard L Boyd Patrick Perlmutter Trevor Lithgow John S Forsythe Google Yue Shi Vinh X Truong Ketav Kulkarni Yue Qu George P Simon Richard L Boyd Patrick Perlmutter Trevor Lithgow John S Forsythe Google Scholar Yue Shi Vinh X Truong Ketav Kulkarni Yue Qu George P Simon Richard L Boyd Patrick Perlmutter Trevor Lithgow John S Forsythe PubMed Yue Shi Vinh X Truong Ketav Kulkarni Yue Qu George P Simon Richard L Boyd Patrick Perlmutter Trevor Lithgow John S Forsythe Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Abstract Peptides based on unnatural β3-amino acids offer a versatile platform for the design of self-assembling nanostructures due to the folding stability of the 14-helix and the high symmetry of the side chains inherent in this geometry. We have previously described that N-terminal acetylation (Ac-) forms a supramolecular self-assembly motif that allows β3-peptides to assemble head-to-tail into a helical nanorod which then further bundles into hierarchical superstructures. Here we investigate the effect of the topography of the 14-helical nanorod on lateral self-assembly. Specifically, we report on the variations in the superstructure of three isomeric peptides comprising the same three β3-amino acid residues: β3-leucine (L), β3-isoleucine (I) β3-alanine (A) to give peptides Ac-β3[LIA], Ac-β3[IAL] and Ac-β3[ALI]. AFM imaging shows markedly different superstructures for the three peptides. Well defined synchrotron far-infrared spectra reveal uniform geometries with a high degree of similarity between the isomeric peptides in the amide modes of the 400–650 wavenumber range. Far-IR also confirms that the C-terminal carboxyl group is free in the assemblies, thus it is solvated in the dispersant. Hence, the differences in the superstructures formed by the fibers are defined primarily by van der Waals energy minimization between the varied cross sectional morphologies of the core nanorods.

Peptides comprised entirely of β-amino acids, or β-peptides, have attracted substantial interest over the past 25 years due to their unique structural and chemical characteristics. β-Peptides form well-defined secondary structures that exhibit different geometries compared with their α-peptide counterparts, giving rise to their foldamer classification. β-Peptide foldamers can be functionalized easily and are metabolically stable and, together with the predictable side-chain topography, have led to the design of a growing number of bioactive β-peptides with a range of biological targets. The strategic engineering of chemical and topographic properties has also led to the design of β-peptide mimics of higher-order oligomers. More recently, the ability of these peptides to self-assemble into complex structures of controlled geometries has been exploited in materials applications. The focus of this mini-review is on how the unique structural features of β-peptide assemblies have been exploited in the design of self-assembled proteomimetic bundles and nanomaterials.