Biomedical subjects

Pilar Redondo

Publications and source records attributed to Pilar Redondo.

5 recordsLinked to original sources

PubMed2006

A combinatorial approach to create artificial homing endonucleases cleaving chosen sequences.

Meganucleases, or homing endonucleases (HEs) are sequence-specific endonucleases with large (>14 bp) cleavage sites that can be used to induce efficient homologous gene targeting in cultured cells and plants. These findings have opened novel perspectives for genome engineering in a wide range of fields, including gene therapy. However, the number of identified HEs does not match the diversity of genomic sequences, and the probability of finding a homing site in a chosen gene is extremely low. Therefore, the design of artificial endonucleases with chosen specificities is under intense investigation. In this report, we describe the first artificial HEs whose specificity has been entirely redesigned to cleave a naturally occurring sequence. First, hundreds of novel endonucleases with locally altered substrate specificity were derived from I-CreI, a Chlamydomonas reinhardti protein belonging to the LAGLIDADG family of HEs. Second, distinct DNA-binding subdomains were identified within the protein. Third, we used these findings to assemble four sets of mutations into heterodimeric endonucleases cleaving a model target or a sequence from the human RAG1 gene. These results demonstrate that the plasticity of LAGLIDADG endonucleases allows extensive engineering, and provide a general method to create novel endonucleases with tailored specificities.

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PubMed2006

Structure and bonding in first-row transition-metal dicarbides: are they related to the stability of met-cars?

First-row transition-metal dicarbides MC(2) (M=Sc-Zn) have been investigated by using quantum-mechanical techniques. The competition between cyclic and linear isomers in these systems has been studied and the bonding scheme for these compounds is discussed through topological analysis of electron density. All of the systems have been found to prefer a C(2v)-symmetric arrangement, although for ZnC(2) the energy difference between this and the linear isomer is rather small. In most cases the C(2v)-symmetric structure corresponds to a T-shaped structure, with the exceptions of TiC(2), CoC(2), and NiC(2) which have been shown to be true rings. A detailed analysis of the variation of the energy of the system with geometry has been carried out. An analysis of the bonding, taking into account the main interactions between the valence orbitals of both fragments, the M atom and the C(2) molecule, has allowed the main features of these compounds to be interpreted. A clear correlation between the dissociation energies of the first-row transition-metal dicarbides and the bonding energies of the corresponding met-cars was observed.

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PubMed2006

Small ScCn cyclic clusters: a density functional study of their structure and stability.

A theoretical study of the ScCn, ScCn+, and ScCn- (n = 1-10) cyclic clusters has been carried out employing the B3LYP density functional method. Predictions for several molecular properties that could help in their possible experimental characterization, such as equilibrium geometries, electronic structures, dipole moments, and vibrational frequencies, are reported. All ScCn cyclic clusters are predicted to have doublet ground states. For cationic clusters the ground state is alternate between singlets (n-even species) and triplets (n-odd members). In the case of anionic clusters the singlet-triplet separation is relatively small, with the singlets being favored in most cases. In general, even-odd parity effects are also observed for different properties, such as incremental binding energies, ionization energies, and electron affinities. For all neutral, cationic, and anionic clusters it is found that cyclic species are more stable than their open-chain counterparts. Therefore, cyclic structures are the most interesting possible targets for an experimental search of scandium-doped carbon clusters.

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PubMed2005

Small carbon clusters doped with early transition metals: a theoretical study of ScCn, ScCn+, and ScCn- (n = 1-8) open-chain clusters.

A theoretical study of the ScCn, ScCn+, and ScCn- (n = 1-8) open-chain clusters has been carried out. Predictions for their electronic energies, rotational constants, dipole moments and vibrational frequencies have been made using the B3LYP method with different basis set including effective core potentials, ECPs. For the ScCn open-chain clusters the lowest-lying states correspond to quartet states for n-odd members, whereas for n-even species the ground state is found to be a doublet. In the cationic and anionic species, the electronic ground state is found to be a singlet for even n and a triplet for odd n. An even-odd parity effect (n-even clusters being more stable than n-odd ones) is observed in neutral and charged clusters. Ionization energies and electron affinities also exhibit a clear parity alternation trend, with n-even clusters having higher values than n-odd ones.

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PubMed2004

On the competition between linear and cyclic isomers in second-row dicarbides.

Second-row dicarbides C(2)X (X = Na-Cl) are investigated with quantum mechanical techniques. The cyclic-linear competition in these systems is studied, and the bonding scheme for these compounds is discussed in terms of the topological analysis of the electronic density. C(2)Na, C(2)Mg, C(2)Al, and C(2)Si are found to prefer a C(2)(v)-symmetric arrangement corresponding to a T-shape structure. On the other hand, for C(2)P, C(2)S, and C(2)Cl the linear isomer is predicted to be the ground state. A detailed analysis of the variation of the electronic energy and orbital energies with the geometry has been carried out. A simple theoretical model, taking into account the main interactions between the valence orbitals of both fragments, the X atom and the C(2) molecule, allows an interpretation of the main features of these compounds.

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