Cationic Geminoid Peptide Amphiphiles Inhibit DENV2 Protease, Furin, and Viral Replication.

Dengue is an important arboviral infectious disease for which there is currently no specific cure. We report gemini-like (geminoid) alkylated amphiphilic peptides containing lysines in combination with glycines or alanines (CHC(O)-Lys-(Gly or Ala)Lys-NHCH, shorthand notation C-KXK-C with X = A or G, and = 0-2). The representatives with 1 or 2 Ala inhibit dengue protease and human furin, two serine proteases involved in dengue virus infection that have peptides with cationic amino acids as their preferred substrates, with IC values in the lower µM range.

Processive catalysis.

Nature's enzymes are an ongoing source of inspiration for scientists. The complex processes behind their selectivity and efficiency is slowly being unraveled, and these findings have spawned many biomimetic catalysts. However, nearly all focus on the conversion of small molecular substrates.

Structure-delivery relationships of lysine-based gemini surfactants and their lipoplexes.

The synthesis and properties of gemini surfactants of the type (R(1)(CO)-Lys(H)-NH)2(CH2)n are reported. For a spacer length of n = 6, the hydrophobic acyl tail was varied in length (R(1) = C8, C10, C12, C14, C16, and C18) and, for R(1) = C18, the degree of unsaturation. For R(1)(CO) = oleoyl (C18:1 Z) the spacer length (n = 2-8) and the stereochemistry of the lysine building block were varied; a 'half-gemini' derivative with a single oleoyl tail and head group was also prepared.

A reagent-based dynamic trigger for cell adhesion, shape change, or cocultures.

The described protocol is a simple and easily implemented method for making dynamic micropatterns for cell culture. It is based on the use of a surface coating material (azido-PLL-g-PEG (APP)) that initially repels cells, but which can be made strongly adherent by addition of a small functional peptide (BCN-RGD) to the cell culture medium. The method can be applied to trigger the adhesion, migration, or shape change of single cells or of populations of cells, and it can be used to create patterned cocultures.

A clamp-like biohybrid catalyst for DNA oxidation.

In processive catalysis, a catalyst binds to a substrate and remains bound as it performs several consecutive reactions, as exemplified by DNA polymerases. Processivity is essential in nature and is often mediated by a clamp-like structure that physically tethers the catalyst to its (polymeric) template. In the case of the bacteriophage T4 replisome, a dedicated clamp protein acts as a processivity mediator by encircling DNA and subsequently recruiting its polymerase.

Functional interlocked systems.

With the advent of supramolecular chemistry and later nanotechnology a great deal of research has been focused on new types of molecular structures, which are not held together by covalent bonds but by non-covalent mechanical interactions. Examples include the catenane, rotaxane, and knot interlocked structures. The design and synthesis of these architectures is an art by itself and as such is worth being reviewed.

Triggering cell adhesion, migration or shape change with a dynamic surface coating.

There's an APP for that: cell-repellent APP (azido-[polylysine-g-PEG]) is used to create substrates for spatially controlled dynamic cell adhesion. The simple addition of a functional peptide to the culture medium rapidly triggers cell adhesion. This highly accessible yet powerful technique allows diverse applications, demonstrated through tissue motility assays, patterned coculturing and triggered cell shape change.

Delivery of DNA and siRNA by novel gemini-like amphiphilic peptides.

We report the design, synthesis, and characterization of a novel type of cationic lipopeptide, gemini-like amphiphilic peptides or 'geminoids'. As an example, the SPKR peptide, inspired by biological nucleic acid binding motifs, was appended with unsaturated (oleoyl/oleyl) alkyl tails. The compound shows remarkable DNA and siRNA delivery, without lysogenic helper lipid, in a variety of cells, with a moderate cytotoxic effect.

Single-step azide introduction in proteins via an aqueous diazo transfer.

The controlled introduction of azides in proteins provides targetable handles for selective protein manipulation. We present here an efficient diazo transfer protocol that can be applied in an aqueous solution, leading to the facile introduction of azides in the side chains of lysine residues and at the N-terminus of enzymes, e.g.

A three-enzyme cascade reaction through positional assembly of enzymes in a polymersome nanoreactor.

Porous polymersomes based on block copolymers of isocyanopeptides and styrene have been used to anchor enzymes at three different locations, namely, in their lumen (glucose oxidase, GOx), in their bilayer membrane (Candida antarctica lipase B, CalB) and on their surface (horseradish peroxidase, HRP). The surface coupling was achieved by click chemistry between acetylene-functionalised anchors on the surface of the polymersomes and azido functions of HRP, which were introduced by using a direct diazo transfer reaction to lysine residues of the enzyme. To determine the encapsulation and conjugation efficiency of the enzymes, they were decorated with metal-ion labels and analysed by mass spectrometry.