Highlights from the 52nd EUCHEM conference on stereochemistry, Bürgenstock, Switzerland, May 2017

The strong wind that was blowing in Brunnen on the 4th of May 2017 was prophetic of the storm of ideas and creativity that would later fall over the participants of the 52nd edition of the Bürgenstock conference. The Bürgenstock conference is a truly unique event. A meeting held in a beautiful and relaxing landscape where the Alps merge with the crystal clear water of the Luzern Lake, researchers from the best Universities, Institutes and companies came to Brunnen for the 52nd Bu¨rgenstock conference from all over the globeR. J. P. and J. M. are very grateful to the organising committee of the 2017 Bürgenstock conference for the award of JSP fellowships. R. J. P is grateful to the Royal Society for a University Research Fellowship. J. M. is grateful to MINECO for a Ramón y Cajal fellowshipS

Synthetic materials at the forefront of gene delivery

This is the Author's Accepted Manuscript of the following article: Lostalé-Seijo, I., & Montenegro, J. (2018). Synthetic materials at the forefront of gene delivery. Nature Reviews Chemistry. doi: 10.1038/s41570-018-0039-1The delivery of nucleic acids with transient activity for genetic engineering is a promising methodology with potential applications in the treatment of diseases ranging from cancer and infectious diseases to heritable disorders. Restoring the expression of a missing protein, correcting defective splicing of transcripts and silencing or modulating the expression of genes are powerful approaches that could have substantial benefits in biological research and medicine. Impressive progress in improving gene delivery has been made in the past decade, and several products have reached the market. However, translating the results of in vitro and preclinical studies into functional therapies is hindered by the suboptimal performance of gene delivery vehicles in capturing, protecting and delivering nucleic acid cargoes safely and efficaciously. Chemistry has a key role in the development of innovative synthetic materials to overcome the challenges of producing next-generation gene delivery therapies and protocols. In this Review, we discuss the latest chemical advances in the production of materials for the delivery of nucleic acids to cells and for gene therapyThe group of J.M. was partially supported by the Spanish Agencia Estatal de Investigación (AEI) (CTQ2014-59646-R and SAF2017-89890-R), the Xunta de Galicia (ED431G/09, ED431C 2017/25 and 2016-AD031) and the European Regional Development Fund (ERDF). J.M. received a Ramón y Cajal grant (RYC-2013-13784), a European Research Council (ERC) Starting Investigator Grant (DYNAP-677786) and a Young Investigator Grant from the Human Frontier Science Research Program (RGY0066/2017)S

1D to 2D Self Assembly of Cyclic Peptides

Despite recent developments in two-dimensional self-assembly, most supramolecular 2D materials are assembled by tedious methodologies, with complex surface chemistry and small sizes. We here report d/l-alternating cyclic peptides that undergo one-dimensional self-assembly into amphiphilic nanotubes, which subsequently arrange as tubular bilayers to form giant nanosheets in the mesoscale. Reversible transitions between the assembled, dispersed, and aggregated states of these nanosheets can be triggered by external stimuli. The characteristic flexibility, defined chemical topology, and length scale of these nanosheets set a clear distinction between this new supramolecular architecture and previously reported 2D nanostructures. The sequential 1D-to-2D self-assembly of peptides described here provides a conceptually new approach to achieve two-dimensional materials with hierarchical organization. These giant nanosheets represent one of the largest 2D supramolecular materials ever made, with potential application as long-range molecular transporters, responsive surfaces, and (bio)sensorsThis work was partially supported by the Spanish Agencia Estatal de Investigación (AEI) [SAF2017-89890-R], the Xunta de Galicia (ED431C 2017/25, 2016-AD031 and Centro Singular de Investigación de Galicia accreditation 2016-2019, ED431G/09), the ISCIII (RD16/0008/003), and the European Union (European Regional Development Fund, ERDF). I.I. thanks the European Commission for a Marie Curie fellowship (MSCA-IF-2018-843332) and the Spanish AEI for a Juan de la Cierva—Formación Fellowship (FJCI-2017-31795). J.M. received a Ramón y Cajal (RYC-2013-13784), an ERC Starting Investigator Grant (DYNAP-677786), and a Young Investigator Grant from the HFSP (RGY0066/2017). We thank Dr. Eugenio Solla, Prof. Juan Granja, Dr. Julian Bergueiro, Dr. Andreas Vargas Jentzsch, and Dr. Mark J. van Raaij for helpful discussions. We also thank Dr. Bergueiro for Figure 1 and Dr. Vargas Jentzsch for assistance with DFT calculationsS

Synthetic Supramolecular Systems in Life-like Materials and Protocell Models

One of the biggest challenges in modern chemistry is the preparation of synthetic materials with life-like behavior for the assembly of artificial cells. In recent years, numerous artificial systems that mimic cellular components and functions have been developed. Supramolecular chemistry plays a key role in such cell mimics given that non-covalent interactions control the shape and function of many biomolecules, such as DNA base pairing, protein structure, ligand-receptor binding, and lipid membrane packing. However, the complexity of living cells constitutes a major challenge for their bottom-up assembly from pure synthetic materials. Inspired by the building blocks of nature, a wide range of supramolecular systems have been developed to reproduce cellular functions such as cell-cell communication, signaling cascades, and dynamic cytoskeleton assemblies. This review surveys a selection of key advances in synthetic derivatives of biomolecules with supramolecular organization and life-like behavior by addressing their non-covalent foundation and integration as increasingly complex protocell modelsThis work was partially supported by the Spanish Agencia Estatal de Investigación (AEI; SAF2017-89890-R), Xunta de Galicia (ED431C 2017/25, 2016-AD031, and ED431G/09), ISCIII (RD16/0008/003), and the European Commission (EC; European Regional Development Fund). I.I. thanks the EC and AEI for MSCA-IF (2018-843332) and JdC (FJCI-2017-31795) fellowships, respectively. J.M. received a Ramón y Cajal grant (RYC-2013-13784), an ERC-Stg grant (DYNAP-677786), and a Young Investigator Grant from the Human Frontier Science Program (RGY0066/2017)S

Metric of a Slow Rotating Body with Quadrupole Moment from the Erez-Rosen Metric

A metric representing a slowly rotating object with quadrupole moment is obtained using a perturbation method to include rotation into the weak limit of the Erez-Rosen metric. This metric is intended to tackle relativistic astrometry and gravitational lensing problems in which a quadrupole moment has to be taken into account

Hydrazone-modulated peptides for efficient gene transfection

Gene transfection continues to be a major challenge in chemistry, biology and materials sciences. New methodologies and recent breakthroughs have renewed the interest in the discovery and development of new tools for efficient gene transfection. Hydrazone formation between a cationic head and hydrophobic tails has emerged as one of the most promising techniques for nucleotide delivery. In this contribution, we have exploited hydrazone formation to modulate the transfection activity of a parent linear peptide in combination with a plasmid DNA cargo. This strategy allowed the straightforward preparation, under physiologically compatible conditions, of a discrete library of amphiphilic modulated penetrating peptides. Without the requirement of any isolation or purification steps, these modulated amphiphilic peptides were combined with a plasmid DNA and screened in transfection experiments of human HeLa cells. Three of these hydrazone-conjugated peptides were identified as excellent vectors for plasmid delivery with comparable, or even higher, efficiencies and lower toxicity than the commercial reagents employed in routine transfection assaysWe are thankful to Dr. Irene Lostalé-Seijo for cell culture assistance and discussions. We acknowledge funding from the Spanish Government MINECO: [CTQ2014-59646-R] and [CTQ2015-74621-JIN], the Xunta de Galicia (ED431G/09), the ERDF and the CESGA. R. G.-F. received a FCT Investigator Grant from Portugal (IF/01133/2015). J.M. received a Ramon y Cajal (RYC-2013-13784) and an ERC Starting Investigator Grant (DYNAP-677786)S

Relacion entre el reconocimiento en la memoria y el contenido del discurso descriptivo en adultos mayores

79 p.La presente investigación se centró en el estudio de la memoria episódica verbal y el discurso descriptivo en adultos mayores entre 60 y 80 años, específicamente en el reconocimiento en la memoria y el contenido en el discurso. Los sujetos fueron sometidos a una prueba de reconocimiento de una lista de palabras y a la descripción de una lámina. El propósito fue determinar: 1) Si el desempeño en el reconocimiento en la memoria y el contenido en el discurso descriptivo varían con la edad y 2) si existe correlación entre estas variables. Los resultados demostraron que el desempeño en el reconocimiento no varía significativamente entre ambos grupos, no así el contenido donde se obtienen diferencias significativas. Por otra parte el análisis indica que estas variables no se correlacionan. Esto significaría que el reconocimiento no sigue el mismo patrón de deterioro que el recuerdo libre en relación con la edad y que las descripciones realizadas por los adultos mayores son breves, menos eficientes y los elementos incluidos dentro de éstas no seguirían una jerarquía clara, lo que justificaría las diferencias de desempeño con los adultos jóvenes

Where in the cell is our cargo? Current methods to study intracellular cytosolic localization

NOTICE: This is the Accepted Version of the following article: Méndez Ardoy, A., Lostalé-Seijo, I., & Montenegro, J. (2018). Where in the cell is our cargo? Current methods to study intracellular cytosolic localization. Chembiochem. doi: 10.1002/cbic.201800390 © 2018 WILEY‐VCH Verlag GmbH & Co. KGaA, WeinheimThe internalization and delivery of active substances into cells is a field of growing interest for chemical biology and therapeutics. As we move from small‐molecule based drugs towards bigger cargos, such as antibodies, enzymes, nucleases or nucleic acids, the development of efficient delivery systems becomes critical for their practical application. Different strategies and synthetic carriers have been developed including cationic lipids, gold nanoparticles, polymers, cell‐penetrating peptides, protein surface modification, etc. However, all these methodologies still present limitations related to the precise targeting of the different intracellular compartments and, in particular, the difficult access to the cellular cytosol. Additionally, the precise quantification of the cellular uptake of a molecule is not enough to demonstrate delivery and/or functional activity. Therefore, methods to determine the cellular distribution of cargos and carriers are of critical importance to identify the barriers that are blocking the activity. In this mini‐review, we survey the different techniques that can be currently used to track and monitor the subcellular localization of the synthetic molecules that we deliver inside cellsWe acknowledge funding from the Spanish Agencia Estatal de Investigación (AEI) [CTQ2014-59646-R, SAF2017-89890-R], the Xunta de Galicia (ED431G/09, ED431C 2017/25 and 2016-AD031) and the ERDF. A. M.-A. received a MCIF from the EC (GLYCONANOPEP-750248). J. M. received a Ramón y Cajal (RYC-2013-13784), an ERC Starting Investigator Grant (DYNAP-677786) and a Young Investigator Grant from the Human Frontier Science Research Program (RGY0066/2017)S

Glycosyl Aldehydes: New Scaffolds for the Synthesis of Neoglycoconjugates via Bioorthogonal Oxime Bond Formation

The straightforward preparation of glycosyl neoconjugates by oxime (or hydrazone) bond formation represents a key bioorthogonal tool in chemical biology. However, when this strategy is employed by reacting the reducing end of the glycan moiety, the configuration and the stereochemical information is lost due to partial (or complete) opening of the glycan cyclic hemiacetal and the formation of the corresponding opened tautomers. We have completed the synthesis of a library of glycosyl aldehydes to be used as scaffold for the synthesis of neoglycoconjugates via oxime bond formation. These glycosyl aldehydes constitute a simple and accessible alternative to avoid loss of chiral information when conjugating, by oxime (or hydrazone) bonds, the aldehyde functionality present at the reducing end of natural carbohydratesThis work was partially supported by the Spanish Agencia Estatal de Investigación (AEI) [CTQ2014–59646-R], the Xunta de Galicia (ED431G/09, ED431C 2017/25 and 2016-AD031) and the ERDF. J.M. received a Ramón y Cajal (RYC-2013–13784), an ERC-Stg (DYNAP- 677786) and a Young Investigator Grant from the Human Frontier Science Research Program (RGY0066/2017)S