Polyoxometalate–peptide hybrid materials: from structure–property relationships to applications

Organo-functionalisation of polyoxometalates (POMs) represents an effective approach to obtain diverse arrays of functional structures and materials, where the introduction of organic moieties into the POM molecules can dramatically change their surface chemistry, charge, polarity, and redox properties. The synergistic combination of POMs and peptides, which perform a myriad of essential roles within cellular biochemistry, including protection and transport in living organisms, leads to functional hybrid materials with unique properties. In this Perspective article, we present the principal synthetic routes to prepare and characterise POM–peptide hybrids, together with a comprehensive description of how their properties – such as redox chemistry, stereochemistry and supramolecular self-assembly – give rise to materials with relevant catalytic, adhesive, and biomedical applications. By presenting the state-of-the-art of the POM–peptide field, we show specifically how emerging chemical approaches can be harnessed to develop tailored POM–peptide materials with synergistic properties for applications in a variety of disciplines

Subcellular localization and therapeutic efficacy of polymeric micellar nanoparticles encapsulating bedaquiline for tuberculosis treatment in zebrafish

The combination drug regimens that have long been used to treat tuberculosis (TB), caused by Mycobacterium tuberculosis, are fraught with problems such as frequent administration, long duration of treatment, and harsh adverse effects, leading to the emergence of multidrug resistance. Moreover, there is no effective preventive vaccine against TB infection. In this context, nanoparticles (NPs) have emerged as a potential alternative method for drug delivery. Encapsulating antibiotics in biodegradable NPs has been shown to provide effective therapy and reduced toxicity against M. tuberculosis in different mammalian models, when compared to conventional free drug administration. Here, we evaluate the localization, therapeutic efficacy and toxic effects of polymeric micellar NPs encapsulating a promising but highly hydrophobic and toxic antitubercular drug bedaquiline (BQ) in zebrafish embryos infected with Mycobacterium marinum. Our study shows that the NP formulation of BQ improves survival and reduces bacterial burden in the infected embryos after treatment when compared to its free form. The intravenously injected BQ NPs have short circulation times due to their rapid and efficient uptake into the endothelial cells, as observed by correlative light and electron microscopy (CLEM)

Interacciones temporales y espaciales de mesocarnívoros simpátricos en una Reserva de la Biosfera: ¿coexistencia o competencia?

Abstract: Temporal and spatial interactions of sympatric mesocarnivores at a Biosphere Reserve: coexistence or competition? Interspecific interactions among tropical mesocarnivorous species and other mammalian trophic guilds have been poorly studied, despite they have important implications in the survival, structure, demography, and distribution of these species. In this study we analyzed spatio-temporal interactions of three sympatric mesocarnivores that are located in the Northeastern limit of their geographic distribution in Mexico, with the objective of analyzing if these species coexist or compete in the axis of the temporal and spatial niche. With a sampling period from January 2015 to December 2016 and 26 camera-trapping stations (with in a set of two camera traps opposite to each other) and located along roads and animal trails, we determined the activity pattern and habitat use of L. wiedii (margay), L. pardalis (ocelote) y P. yagouaroundi (yaguarundi). All independent photographs of each species were grouped into three temporal categories (day, night and twilight) and six habitat categories; Oak Forest, Oak-Pine Forest, Cloud Forest, Pine-Oak Forest, Tropical Deciduous Forest and Medium Forest. Temporal and spatial overlap between species (i.e. interactions) was obtained with the Czekanowski index and the Pianka index, respectively. These indices are symmetrical and take values from zero to one, where the results close to zero indicate that there is no overlap between species and values close to one indicate overlap. We obtained a total of 379 independent photographs, of which 239 corresponded to margay, 118 to ocelot and 22 to yaguarundi. Margay and ocelot were nocturnal, with 75 % of their records in this category showing a high temporal overlap (0.85); whereas yaguarundi was fully diurnal, suggesting it may be able to coexist with the other two species (margay and ocelot). Moreover, the yaguarundi used habitat similar to ocelot and margay (with high spatial overlap of 0.81 and 0.72, respectively), while the spatial overlap between the margay and ocelot was intermediate (0.53), since they used in most cases different habitat types. Our results suggest that there is no interspecific competition among these tropical mesocarnivorous species, probably due to antagonistic interactions among them on the temporal and spatial axis. These strategies may positively favor populations of mesocarnivores, which are characterized by having a high territorial behavior. Rev. Biol. Trop. 66(3): 996-1008. Epub 2018 September 01. Key words: “El Cielo” Biosphere Reserve; Tamaulipas; Mexico; tropical felines; interespecific interaction

Micelas sensibles a pH basadas en polipeptidos sintéticos para aplicaciones en biomedicina

Máster en Materiales Nanoestructurados para Aplicaciones Nanotecnológicas (Nanostructured Materials for Nanotechnology Applications).During the past few decades, nanotherapy has proposed a plethora of drug carriers to address serious illnesses such us cancer. These vehicles are, normally, decorated with biomolecules with the aim of delivering their cargo to specific places in the organisms, such as tumoural microenvironments. Nevertheless, when a nanoparticle is introduced into a biological media, it gets covered by a layer of biomolecules, the so-called protein corona. This organic coating diminishes the circulation time and facilitates its excretion. Therefore, an alternative nanoparticle design should be proposed to reduce such recognition. Herein, what is proposed is that a sudden change on the outer shell of the particle would disrupt the protein adhesion, improving both cellular uptake and circulation times. Among all these possible strategies, the slightly lower pH, in the cancer tissue, could be used to provoke such transformation and therefore reduce the protein adhesion. In this project, two different micellar systems, based on synthetic block copolypeptides, were prepared to face off such disruption. The first one is based on poly (glutamic acid) as hydrophilic block, whose conformational change, under acidic pH, would make the micelle instable, avoiding the protein coating. While the other one, based on poly (DMMA-lysine), would rapidly change their surface charge from negative to positive due to a chemical deprotection, and therefore the protein interaction would be interrupted. Block copolypeptides were synthesised monodisperse and in high yields. In addition, the subsequent prepared micellar formulations were successfully isolated and in a very feasible way. Interestingly, different aggregates could be selectively prepared in a controlled and reproducible way, depending on the polymer structure and the fabrication method. The aggregates were found to be pH responsive based on DLS, -potential and circular dichroism studies.Peer reviewe

Suppressing catalyst poisoning in the carbodiimide-fueled reaction cycle

In biology, cells regulate the function of molecules using catalytic reaction cycles that convert reagents with high chemical potential (fuel) to waste molecules. Inspired by biology, synthetic analogs of such chemical reaction cycles have been devised, and a widely used catalytic reaction cycle uses carboxylates as catalysts to accelerate the hydration of carbodiimides. The cycle is versatile and easy to use, so it is widely applied to regulate motors, pumps, self-assembly, and phase separation. However, the cycle suffers from side reactions, especially the formation of N-acylurea. In catalytic reaction cycles, side reactions are disastrous as they decrease the fuel’s efficiency and, more importantly, destroy the molecular machinery or assembling molecules. To put that in perspective, a side reaction that irreversibly converts as little as 1% of the fuel into a side product would mean less than 5% of the molecular machine left after 100 cycles. Therefore, this work tested how to suppress N-acylurea by screening precursor concentration, its structure, carbodiimide structure, additives, temperature, and pH. It turned out that the combination of low temperature, low pH, and 10% pyridine as a fraction of the fuel could significantly suppress the N-acylurea side product and keep the reaction cycle highly effective to regulate successful assembly. We anticipate that our work will provide guidelines for using carbodiimide-fueled reaction cycles to regulate molecular function about how to choose an optimal condition

Rational design and self-assembly of polyoxometalate-peptide hybrid materials

The synergistic combination between biomolecules and polyoxometalates (POMs) has recently been considered as an effective approach to construct nano-biomaterials with diverse structures and morphologies toward biological applications. Different synthetic routes for the preparation and characterization of covalent POM-peptide hybrids are discussed within the first part of this chapter, together with a comprehensive description of some of their unique properties such as stereochemistry and self-assembly ability. The second part is devoted to ionic compounds that have been used as catalysts and adhesive materials and have shown interesting biomedical and antimicrobial applications.N

Automated fabrication of polypeptide micelles as carriers for hydrophobic drugs

Resumen del trabajo presentado a la Bordeaux Polymer Conference (BPC), celebrada en Bordeaux (Francia) del 28 al 31 de mayo de 2018.Block copolypeptides are excellent candidates to perform drug delivery applications, due their biocompatibility. Furthermore, they are easily prepared via ring opening polyring polymerization (ROP) from their corresponding protected N-carboxyanhydrides, which after a deprotection step give rise to amphiphilic block copolypetides.Peer Reviewe

Fast and controlled Ring-Opening Polymerization of N-carboxyanhydrides via a cooperative bifunctional amino acid

The Ring-Opening Polymerization (ROP) of amino acid N-Carboxyanhydrides (NCAs) offers a straightforward method for preparing polypeptide-like polymers that display characteristics of their natural counterparts, e.g. secondary structure, and enables rapid in vitro screenings. Although recent publications have progressed in achieving water tolerance, a universally user-friendly solu-tion has yet to be achieved. In this communication, we provide a new polymerization set-up that uses an amino acid salt as an initiator. The bifunctional initiator is key for a fast and controlled polymerization, as the carboxylate opens the NCA in the initiation step, and the acyl group is fur-ther transferred to the nitrogen atom in the amine functionality via a concerted low-barrier mecha-nism. Then, it undergoes accelerated chain propagation via the newly generated carbamate rest in the N-acylated chain, as revealed by theoretical calculations at the DFT level and experimental observations. The fast polymerization kinetics enables the polymerization process to be carried out even in the presence of water. In addition, different amino acids can be used as initiators. The concerted O→N acyl shift and the fast and controlled kinetics shed light on cooperative initiating phenomena

Charge conversion nanocarriers based on amphiphilic polypetides

Trabajo presentado al European Congress and Exhibition on Advanced Materials and Processes (EUROMAT), celebrado en Tesalónica (Grecia9 del 17 al 22 de septiembre de 2017.Peer Reviewe

Polyoxometalate-polypeptide nanoassemblies as peroxidase surrogates with antibiofilm properties

Developing artificial metalloenzymes that possess a superior performance to their natural counterparts is an attractive concept. Polyoxometalates (POMs) are a class of anionic molecular metal–oxides with excellent redox properties and bioactivity. We have recently introduced “POMlymers” – covalently conjugated POM–peptide hybrid materials – where the polypeptide chain is obtained through a ring-opening polymerisation (ROP) of α-amino acid N-carboxyanhydrides (NCA) on an inorganic POM scaffold. Attracted by the idea of preparing artificial metalloenzymes, here we report the supramolecular self-assembly of POMlymer hybrids into nanoparticles where an optimal environment for catalysis is created. Our results demonstrate that the self-assembly of covalent POMlymers, enhances the peroxidase-like activity of the parent POM anion whereas, in contrast, the catalytic activity for nanoparticles obtained by ionic self-assembly of the same peptide and POM components practically disappears. Furthermore, POMlymer nanoparticles also present antimicrobial and antibiofilm activity against the skin bacterium Staphylococcus epidermidis; whereas, ionic POM–peptide hybrids significantly increase biofilm production and endogenous production of reactive oxygen species. In summary, we present the self-assembly of POMlymer hybrids into nanoparticles and a combination of peroxidase activity and microbiology assays that show that the POM–peptide covalent bond is essential for the stability of the self-assembled nanoparticles and therefore for their catalytic and biological activity.This work was funded through the grant PID2019-109333RB-I00 funded by MCIN/AEI/10.13039/501100011033 (Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación, Spain), through project LINKA20270 i-Link+ 2019 funded by CSIC and through Fondo Social de la DGA (grupo DGA E15_20R). HSC is grateful for a predoctoral fellowship FPU2016/02456 funded by Ministerio de Universidades (Spain). E. A. B. and S. G. M. acknowledge funding from the European Union's Horizon 2020 research and innovation program (Marie Skłodowska-Curie grant agreement no. 845427).Peer reviewe