Exo-chirality of the α-helix.

The structure of helical polymers is dictated by the molecular chirality of their monomer units. Particularly, macromolecular helices with monomer sequence control have the potential to generate chiral topologies. In α-helical folded peptides, the sequential repetition of amino acids generates a chiral layer defined by the amino acid side chains projected outside the amide backbone.

High-throughput nephelometry methodology for qualitative determination of aqueous solubility of chemical libraries.

The purpose of the protocol reported in this work is the solubility profiling of large chemical libraries using nephelometry. This technique allows the qualitative classification of compounds as highly, moderately, or poorly water-soluble. The described methodology is not intended to yield quantitative solubility values of the studied compounds but can be used as a primary solubility assessment of large chemical libraries, to guide hit prioritization after High Throughput Screening (HTS) campaigns.

Liposome fusion with orthogonal coiled coil peptides as fusogens: the efficacy of roleplaying peptides.

Biological membrane fusion is a highly specific and coordinated process as a multitude of vesicular fusion events proceed simultaneously in a complex environment with minimal off-target delivery. In this study, we develop a liposomal fusion model system with specific recognition using lipidated derivatives of a set of four designed heterodimeric coiled coil (CC) peptide pairs. Content mixing was only obtained between liposomes functionalized with complementary peptides, demonstrating both fusogenic activity of CC peptides and the specificity of this model system.

Influence of Membrane-Fusogen Distance on the Secondary Structure of Fusogenic Coiled Coil Peptides.

Liposomal membrane fusion is an important tool to study complex biological fusion mechanisms. We use lipidated derivatives of the specific heterodimeric coiled coil pair E: (EIAALEK) and K: (KIAALKE) to study and control the fusion of liposomes. In this model system, peptides are tethered to their liposomes via a poly(ethylene glycol) (PEG) spacer and a lipid anchor.

Membrane-Fusogen Distance Is Critical for Efficient Coiled-Coil-Peptide-Mediated Liposome Fusion.

We have developed a model system for membrane fusion that utilizes lipidated derivatives of a heterodimeric coiled-coil pair dubbed E (EIAALEK) and K (KIAALKE). In this system, peptides are conjugated to a lipid anchor via a poly(ethylene glycol) (PEG) spacer, and this contribution studies the influence of the PEG spacer length, coupled with the type of lipid anchor, on liposome-liposome fusion. The effects of these modifications on peptide secondary structure, their interactions with liposomes, and their ability to mediate fusion were studied using a variety of different content mixing experiments and CD spectroscopy.