Interacció intermolecular NH3-NH3: Petits clústers d'amoníac, (NH3)2-5, i amoníac líquid

Treballs Finals de Grau de Química, Facultat de Química, Universitat de Barcelona, Any: 2015, Tutora: Margarita Albertí WirsingMolecular Dynamics (MD) is a simulation technique that allows to analyse the interactions between atoms and molecules along the time, giving a visualization of the movement of the particles. For this simulation, an energy potential model describing the interaction needs to be implemented in MD programmes, giving us information directly comparable with experimental behaviour. MD simulations not only are useful for comparative purposes but also for predictive ones. Obviously, if we want to make predictions with a high guarantee of success, the model must be accurate. However, in order to reduce the simulation computational cost, the model has to be as simple as possible. Ammonia is one of the most important compounds in nature because it contributes significantly to the nutritional needs of living organisms. In recent years, there have been a large number of accurate theoretical as well as experimental investigations on small ammonia clusters interactions, but not so many about liquid ammonia. In order to represent big systems with lots of molecules (as required to simulate liquids), it is very important to have a function describing as good as possible the intermolecular interactions. In MD the previous interaction is often expressed as a sum of electrostatic and non electrostatic interaction contributions. The electrostatic one is usually defined by the Coulomb’s law equation, whereas the non electrostatic one is often given by the Lennard Jones (LJ) potential. The LJ function, although it is quite good and widely used in MD simulations, it presents some problems. It is too repulsive at short distances, and too attractive at long distances. For this reason, the present TFG focuses on the study of ammonia using a modified LJ potential energy function (ILJ) to describe the non electrostatic contribution. The ammonia study, according to the different properties of small clusters and liquid ammonia, has been divided in two parts. In the first one, the binding energy and equilibrium geometry of some small clusters, (NH3)2-5, have been calculated using the ILJ function and the results have been compared with other theoretical as well as experimental data. In the second part, once the reliability of the potential energy function has been proved, it has been applied to investigate some characteristics of liquid ammonia. In particular, the evolution of the density values and of the diffusion coefficients with the temperature has been analysed. Moreover some structural properties of liquid ammonia have been compared with X-ray and neutron diffraction experimental data

Encoded chemical libraries: exploring dynamic and evolvable libraries leveraged on PNA-tagging

This thesis has been divided into four projects exploring various applications of peptide nucleic acids (PNA) in library screenings and DNA detection. The first two projects used PNA to improve previously reported screening strategies: dynamic combinatorial libraries (DCLs) and DNA-encoded chemical libraries (DELs). The other two projects were motivated by the imminent need to understand, detect, and neutralize the SARS-CoV-2 during the COVID-19 pandemic. This led us to study the immunodominant linear epitopes of SARS-CoV-2 very early on in the outbreak, and to develop a dual-readout DNA-detection method for SARS-CoV-2 later on

The RB596 antibody recognizes a linear epitope from the spike S protein from SARS-CoV-2

The recombinant antibody RB596 recognizes a linear epitope (residues 973-984, ISSVLNDILSRL) from the SARS-CoV-2 spike S protein

Pseudo-Complementary G:C Base Pair for Mixed Sequence dsDNA Invasion and Its Applications in Diagnostics (SARS-CoV-2 Detection)

Pseudo-complementary oligonucleotides contain artificial nucleobases designed to reduce duplex formation in the pseudo-complementary pair without compromising duplex formation to targeted (complementary) oligomers. The development of a pseudo-complementary A:T base pair, Us:D, was important in achieving dsDNA invasion. Herein, we report pseudo-complementary analogues of the G:C base pair leveraged on steric and electrostatic repulsion between the cationic phenoxazine analogue of cytosine (G-clamp, C+) and N-7 methyl guanine (G+), which is also cationic. We show that while complementary peptide nucleic acids (PNA) form a much more stable homoduplex than the PNA:DNA heteroduplex, oligomers based on pseudo-C:G complementary PNA favor PNA:DNA hybridization. We show that this enables dsDNA invasion at physiological salt concentration and that stable invasion complexes are obtained with low equivalents of PNAs (2–4 equiv). We harnessed the high yield of dsDNA invasion for the detection of RT-RPA amplicon using a lateral flow assay (LFA) and showed that two strains of SARS-CoV-2 can be discriminated owing to single nucleotide resolution

Experimental Identification of Immuno- dominant B-cell Epitopes from SARS-CoV-2

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the current public health crisis with devastating consequences to our societies. This COVID-19 pandemic has become the most serious threat to global public health in recent history. Given the unprecedented economic and social impact that it is causing, identification of immunodominant epitopes from SARS-CoV-2 is of great interest, not only to gain better insight into the adaptive immune response, but also for the development of vaccines, treatments and diagnostic tools. In this review, we summarize the already published or preprinted reports on the experimental identification of B-cell linear epitopes of SARS-CoV-2 proteins. Six different epitopes leading to neutralizing antibodies have been identified. Moreover, a summary of peptide candidates to be used for diagnostic tools is also included

Combining recombinase polymerase amplification and DNA-templated reaction for SARS-CoV-2 sensing with dual fluorescence and lateral flow assay output

The early phase of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic was exacerbated by a diagnostic challenge of unprecedented magnitude. In the absence of effective therapeutics or vaccines, breaking the chain of transmission through early disease detection and patient isolation was the only means to control the growing pandemic. While polymerase chain reaction (PCR)-based methods and rapid-antigen tests rose to the occasion, the analytical challenge of rapid and sequence-specific nucleic acid-sensing at a point-of-care or home setting stimulated intense developments. Herein we report a method that combines recombinase polymerase amplification and a DNA-templated reaction to achieve a dual readout with either fluorescence (microtiter plate) or naked eye (lateral flow assay: LFA) detection. The nucleic acid templated reaction is based on an SNAr that simultaneously transfers biotin from one Peptide Nucleic Acid (PNA) strand to another PNA strand, enabling LFA detection while uncaging a coumarin for fluorescence readout. This methodology has been applied to the detection of a DNA or RNA sequence uniquely attributed to the SARS-CoV-2

PNA-Based Dynamic Combinatorial Libraries (PDCL) and screening of lectins

International audienc

Dual Bcl-XL /Bcl-2 inhibitors discovered from DNA-encoded libraries using a fragment pairing strategy

A dual Bcl-XL / Bcl-2 inhibitor was discovered from DNA-encoded libraries using a two steps process. In the first step, DNA was used to pair PNA-encoded fragments exploring > 250 000 combinations. In the second step, a focused library combining the selected fragments with linkers of different lengths and geometries led to the identification of tight binding adducts that were further investigated for their selective target engagement in pull-down assays, for their affinity by SPR, and their selectivity in a cytotoxicity assay. The best compound showed comparable cellular activity to venetoclax, the first-in-class therapeutic targeting Bcl-2