Constrained cell penetrating peptides.

In this review we provide an overview of recent developments in the field of cell penetrating peptides (CPPs) on research that aims to achieve better control over their transduction properties - one of the big challenges - by means of restraining them. Three different constraining strategies are presented: triggerable activation, backbone rigidification and macrocyclization. Each of these methods have their opportunities in gaining control over CPP activity and selectivity.

Molecular tools for the construction of peptide-based materials.

Proteins and peptides are fundamental components of living systems where they play crucial roles at both functional and structural level. The versatile biological properties of these molecules make them interesting building blocks for the construction of bio-active and biocompatible materials. A variety of molecular tools can be used to fashion the peptides necessary for the assembly of these materials. In this tutorial review we shall describe five of the main techniques, namely solid phase peptide synthesis, native chemical ligation, Staudinger ligation, NCA polymerisation, and genetic engineering, that have been used to great effect for the construction of a host of peptide-based materials.

Sensing cell adhesion using polydiacetylene-containing peptide amphiphile fibres.

Sensing cell adhesion by means of a colourimetric response provides an intuitive measure of cell binding. In this study polydiacetylene-containing peptide amphiphiles fibres were designed to sense cell adhesion by means of a colour change. The diacetylene-containing peptide amphiphiles were functionalised with the cell-binding motif RGDS, and subsequently mixed with non-functionalised diacetylene-containing spacer amphiphiles. The diacetylenes in the backbone of these fibres were polymerised using UV-light to give dark blue fibre solutions. Subsequent cell adhesion induced a colour change from blue to pink. The propensity of the RGDS fibres to change colour upon cell adhesion could be tuned by varying the C-terminal amino acid of the spacer amphiphile. In addition to this, by varying the RGDS density we found that the optimum colourimetric response was obtained for fibres with a 6 : 1 ratio of non-RGDS to RGDS amphiphiles.

A structural study of the self-assembly of a palmitoyl peptide amphiphile.

Peptide amphiphiles consisting of a hydrophobic alkyl tail coupled to the eight-amino acid GANPNAAG have been studied extensively for their fibre forming properties. However, detailed characteristics of the fibre structure, such as peptide conformation and molecular organisation, are unknown to date. In this report a range of characterization techniques is described that have been employed to elucidate the internal structure of these fibres. Based on the results obtained by circular dichroism spectroscopy, X-ray diffraction and solid state NMR spectroscopy it was concluded that in a self-assembled state the peptide is in a stretched beta-sheet conformation, with the alkyl tails interdigitated and hydrogen-bonded along the axis of the fibre.

Synthesis, aggregation, and binding behavior of synthetic amphiphilic receptors.

Amphiphilic bowl-shaped receptor molecules have been synthesized starting from diphenylglycoluril. Upon dispersion in water, these molecules self-assemble to form vesicles that bind neutral guests and alkali metal ions. In the case of bis(alkylester)-modified receptor compound 4, electron microscopy reveals that an increase in the size of the alkali metal ion (from Na(+) or K(+) to Rb(+) and to Cs(+)) leads to a change in the shape of the aggregates, viz. from vesicles to tubules. Monolayer experiments suggest that this behavior is due to a change in the conformation of this amphiphilic receptor. In water, molecules of 4 have an elongated conformation that changes to a sandwich-like one upon binding of alkali metal ions. Binding studies with vesicles from the bis-ammonium receptors 6 and 9 and the guest 4-(4-nitrophenylazo)resorcinol (Magneson) reveal that below the critical aggregation concentration (CAC) of the amphiphile 1:1 host-guest complexes are formed with high host-guest association constants. Above the CAC, a host-guest ratio of 2:1 was observed that indicates that only the cavities on the outside of the vesicle can be occupied. In the case of the naphthalene walled compound 8 changes in the vesicle structure are induced by the organic guest Magneson.