Cross-priming allows dendritic cells (DCs) to induce cytotoxic T cell (CTL) responses to extracellular antigens. DCs require cognate 'licensing' for cross-priming, classically by helper T cells. Here we demonstrate an alternative mechanism for cognate licensing by natural killer T (NKT) cells recognizing microbial or synthetic glycolipid antigens. Such licensing caused cross-priming CD8alpha(+) DCs to produce the chemokine CCL17, which attracted naive CTLs expressing the chemokine receptor CCR4. In contrast, DCs licensed by helper T cells recruited CTLs using CCR5 ligands. Thus, depending on the type of antigen they encounter, DCs can be licensed for cross-priming by NKT cells or helper T cells and use at least two independent chemokine pathways to attract naive CTLs. Because these chemokines acted synergistically, this can potentially be exploited to improve vaccinations.

The use of peptidomimetics has emerged as a powerful means for overcoming the limitations inherent in the physical characteristics of peptides thus improving their therapeutic potential. A peptidomimetic approach that has emerged in recent years with significant potential, is the use of beta-amino acids. Beta-amino acids are similar to alpha-amino acids in that they contain an amino terminus and a carboxyl terminus. However, in beta-amino acids two carbon atoms separate these functional termini. beta-amino acids, with a specific side chain, can exist as the R or S isomers at either the alpha (C2) carbon or the beta (C3) carbon. This results in a total of 4 possible diastereoisomers for any given side chain. The flexibility to generate a vast range of stereo- and regioisomers, together with the possibility of disubstitution, significantly expands the structural diversity of beta-amino acids thereby providing enormous scope for molecular design. The incorporation of beta-amino acids has been successful in creating peptidomimetics that not only have potent biological activity, but are also resistant to proteolysis. This article reviews the rapidly expanding applications of beta-amino acids in the design of bioactive peptide analogues ranging from receptor agonists and antagonists, MHC-binding peptides, antimicrobial peptides and peptidase inhibitors. Given their structural diversity taken together with the ease of synthesis and incorporation into peptide sequences using standard solid-phase peptide synthesis techniques, beta-amino acids have the potential to form a new platform technology for peptidomimetic design and synthesis.

From little things big things grow: 14‐Helical N‐acetyl β3‐peptides spontaneously self‐assemble in a unique head‐to‐tail fashion to form fibers from solution. The fiber size can be controlled from the nano‐ to the macroscale. The inherent flexibility in design and ease of synthesis provide powerful new avenues for the development of novel bio‐ and nanomaterials by supramolecular self‐assembly.

Hybrid peptides consisting of alpha-amino acids with judiciously placed beta-amino acids show great promise as peptidomimetics in an increasing range of therapeutic applications. This reflects a combination of increased stability, high specificity and relative ease of synthesis.

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.

With recent advances in the design and delivery of peptide-based therapeutics there has been a growing interest on the use of peptides in vaccine design. Moreover, functional dissection and proteomic analysis of the immunogenic epitopes of proteins from pathogenic micro-organisms, cancers and self-tissues targeted by autoimmune responses, have broadened the range of target epitopes and given clues to enhancing peptide immunogenicity. Consistent with these observations; peptides can be synthesised with defined chemical modifications to mimic natural epitopes and/or deliberately introduce protease resistant peptide bonds to regulate their processing independent of tissue specific proteolysis and to stabilize these compounds in vivo. We discuss the potential of peptide-based vaccines for the treatment of chronic viral diseases and cancer and review recent developments in the field of epitope discovery and peptide-based vaccines.

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.

Regio-isomeric effects on the oxidative stability of triacylglycerols (TAG) containing docosahexaenoic acid (DHA) were investigated using two pairs of regio-isomerically pure TAG, namely 1,3-dihexadecanoyl-2-(4,7,10,13,16,19-docosahexaenoyl)glycerol (PDP)/1,2-dihexadecanoyl-3-(4,7,10,13,16,19-docosahexaenoyl)glycerol (PPD) and 1,3-dioctadecenoyl-2-(4,7,10,13,16,19-docosahexaenoyl)glycerol (ODO)/1,2-dioctadecenoyl-3-(4,7,10,13, 16,19-docosahexaenoyl)glycerol (OOD) where P, O, and D represent palmitic acid, oleic acid, and DHA respectively. Each pair of regio-isomers was subjected to accelerated auto-oxidation (at 40 or 50°C inside a dark oven). In each case, the TAG oxidized more slowly when DHA was located at the sn-2 position (PDP and ODO) compared to the sn-1(3) position (PPD and OOD), as evidenced by slower development of peroxide value, slower depletion of DHA, and slower generation of secondary oxidation products propanal and trans, trans-2,4-heptadienal. The positional effect on auto-oxidation was more pronounced when DHA occurred in combination with oleic acid than with palmitic acid.