Biomimetic Generation and Remodeling of Phospholipid Membranes by Dynamic Imine Chemistry.

Biomimetic liposomes have a wide array of applications in several areas, ranging from medicinal chemistry to synthetic biology. Due to their biocompatibility and biological relevance, there is particular interest in the formation of synthetic phospholipid vesicles and the development of methods to tune their properties in a controlled manner. However, while true biological membranes are capable of responding to environmental stimuli by enzymatically remodeling their composition, synthetic liposomes are typically static once formed. Herein we report the chemoselective reaction of the natural amine-containing lysosphingomyelin with a series of long-chain aldehydes to form imines. This transformation results in the formation of phospholipid liposomes that are in dynamic equilibrium with the aldehyde-amine form. The reversibility of the imine linkage is exploited in the synthesis of vesicles that are capable of responding to external stimuli such as temperature or the addition of small molecules.

Versatile symport transporters based on cyclic peptide dimers.

We present the synthesis and transmembrane transport properties of a new family of tris-pyridine-decorated cyclic peptides. These molecules are designed to self-assemble into dimeric shuttles in nonpolar media, which act as symport ionophores in which, apparently, the tris-pyridine scaffold complexes both cations and anions with high potency and efficacy.

Supramolecular functional assemblies: dynamic membrane transporters and peptide nanotubular composites.

The fabrication of functional molecular devices constitutes one of the most important current challenges for chemical sciences. The complex processes accomplished by living systems continuously demand the assistance of non-covalent interactions between molecular building blocks. Additionally, these building blocks (proteins, membranes, nucleotides) are also constituted by self-assembled structures. Therefore, supramolecular chemistry is the discipline required to understand the properties of the minimal self-assembled building blocks of living systems and to develop new functional smart materials. In the first part of this feature article, we highlight selected examples of the preparation of supramolecular membrane transporters with special emphasis on the application of dynamic covalent bonds. In the second section of the paper we review recent breakthroughs in the preparation of peptide nanotube hybrids with functional applications. The development of these devices constitutes an exciting process from where we can learn how to understand and manipulate supramolecular functional assemblies.

Self-assembling Venturi-like peptide nanotubes.

We describe the design and synthesis of self-assembling peptide nanotubes that have an internal filter area and whose length and internal diameters, at the entrance and in the constricted area, are precisely controlled.

Bioinspired Artificial Sodium and Potassium Ion Channels.

In Nature, all biological systems present a high level of compartmentalization in order to carry out a wide variety of functions in a very specific way. Hence, they need ways to be connected with the environment for communication, homeostasis equilibrium, nutrition, waste elimination, etc. The biological membranes carry out these functions; they consist of physical insulating barriers constituted mainly by phospholipids. These amphipathic molecules spontaneously aggregate in water to form bilayers in which the polar groups are exposed to the aqueous media while the non-polar chains self-organize by aggregating to each other to stay away from the aqueous media. The insulating properties of membranes are due to the formation of a hydrophobic bilayer covered at both sides by the hydrophilic phosphate groups. Thus, lipophilic molecules can permeate the membrane freely, while the small charged or very hydrophilic molecules require the assistance of other membrane components in order to overcome the energetic cost implied in crossing the non-polar region of the bilayer. Most of the large polar species (such as oligosaccharides, polypeptides or nucleic acids) cross into and out of the cell via endocytosis and exocytosis, respectively. Nature has created a series of systems (carriers and pores) in order to control the balance of small hydrophilic molecules and ions. The most important structures to achieve these goals are the ionophoric proteins that include the channel proteins, such as the sodium and potassium channels, and ionic transporters, including the sodium/potassium pumps or calcium/sodium exchangers among others. Inspired by these, scientists have created non-natural synthetic transporting structures to mimic the natural systems. The progress in the last years has been remarkable regarding the efficient transport of Na(+) and K(+) ions, despite the fact that the selectivity and the ON/OFF state of the non-natural systems remain a present and future challenge.

Membrane-targeted self-assembling cyclic peptide nanotubes.

Peptide nanotubes are novel supramolecular nanobiomaterials that have a tubular structure. The stacking of cyclic components is one of the most promising strategies amongst the methods described in recent years for the preparation of nanotubes. This strategy allows precise control of the nanotube surface properties and the dimensions of the tube diameter. In addition, the incorporation of 3- aminocycloalkanecarboxylic acid residues in the nanotube-forming peptides allows control of the internal properties of the supramolecular tube. The research aimed at the application of membrane-interacting self-assembled cyclic peptide nanotubes (SCPNs) is summarized in this review. The cyclic peptides are designed to interact with phospholipid bilayers to induce nanotube formation. The properties and orientation of the nanotube can be tuned by tailoring the peptide sequence. Hydrophobic peptides form transmembrane pores with a hydrophilic orifice, the nature of which has been exploited to transport ions and small molecules efficiently. These synthetic ion channels are selective for alkali metal ions (Na(+), K(+) or Cs(+)) over divalent cations (Ca(2+)) or anions (Cl(-)). Unfortunately, selectivity was not achieved within the series of alkali metal ions, for which ion transport rates followed the diffusion rates in water. Amphipathic peptides form nanotubes that lie parallel to the membrane. Interestingly, nanotube formation takes place preferentially on the surface of bacterial membranes, thus making these materials suitable for the development of new antimicrobial agents.

Comparison of the clinical effect of the adhesive strategies of universal adhesives in the treatment of non-carious cervical lesions: systematic review and meta-analysis

Objective: to compare, through a systematic review and a meta-analysis, the clinical effect of the adhesive strategies of universal adhesives (UA) in the treatment of non-carious cervical lesions (NCCLs). material and method: a search of the literature was carried out up to january 2018, in the biomedical databases: Pubmed, Embase, Scielo, Science Direct, SIGLE, LILACS, BBO, Google Scholar and the Central Register of Cochrane Clinical Trials. the selection criteria of the studies were as: randomized clinical trials, with a maximum age of 5 years and which report the clinical effects (marginal adaptation, discoloration or marginal staining, presence of secondary caries, postoperative sensitivity, retention and fractures) of the UA in the treatment of NCCLs. the risk of study bias was analyzed through the Cochrane Handbook of systematic reviews of interventions. results: the search strategy resulted in eight articles that reported no difference in marginal adaptation, discoloration or marginal staining, presence of secondary caries and postoperative sensitivity among the adhesive strategies of the UA; however they reported a difference between the retention and the presence of fractures, with the conventional adhesive strategy resulting in a better clinical effect. conclusion: the reviewed literature suggests that the conventional adhesive strategy of UAs results in greater retention and absence of fractures in the treatment of NCCLs.