Synthesis of Copper-64 and Technetium-99M Labeled Oligonucleotides with Macrocyclic Ligands

Abstract

An efficient procedure for the preparation of oligonucleotides carrying a mono-N-substituted azamacrocycle and its radiolabeled complex with Cu-64 and Tc-99m is reported. The new derivatives are of potential interest for Positron Emission Tomography and Single Photon Emission Tomography.     

A Monoclonal Antibody that Specifically Recognizes m'A Nucleoside

Abstract

A hybridoma against the nucleoside m⁶A has been obtained from mouse spleen. This hybridoma was named H65 and it secretes monoclonal antibodies anti-m⁶A. The competition assays showed that the monoclonal antibody was highly specific for m⁶A nucleoside.     

Note: A Convenient Method for the Preparation of N2, N2-Dimethylguanosine

Abstract

The preparation of N², N²-dimethylguanosine is described. The use of the 2-(p-nitrophenyl)ethyl group instead of the benzyl protecting group for the O⁶ position of the guanine ring resulted in better yields and shorter protocols.     

Use of a Base-Labile Protected Derivative of 6-Mercaptohexanol for the Preparation of Oligonucleotides Containing a Thiol Group at the 5′-End

Abstract

The preparation of a base-labile (Dnpe) protected derivative of 6-mercaptohexanol is described. The use of the phosphoramidite derivative of this compound improves both yields and the time needed for the preparation of oligonucleotides containing a thiol group at the 5′-end.     

Rational design of the survivin/CDK4 complex by combining protein–protein docking and molecular dynamics simulations

Survivin, the smallest inhibitor of apoptosis protein (IAP), is a valid target for cancer research. It mediates both the apoptosis pathway and the cell cycle and has been proposed to form a complex with the cyclin-dependent kinase protein CDK4. The resulting complex transports CDK4 from the cytosol to the nucleus, where CDK4 participates in cell division. Survivin has been recognized as a node protein that interacts with several partners; disruption of the formed complexes can lead to new anticancer compounds. We propose a rational model of the survivin/CDK4 complex that fulfills the experimental evidence and that can be used for structure-based design of inhibitors modifying its interface recognition. In particular, the suggested complex involves the alpha helical domain of survivin and resembles the mode of binding of survivin in the survivin/borealin X-ray structure. The proposed model has been obtained by combining protein–protein docking, fractal-based shape complementarity, electrostatics studies and extensive molecular dynamics simulations.

Landscape Genetics of Leaf-Toed Geckos in the Tropical Dry Forest of Northern Mexico

Habitat fragmentation due to both natural and anthropogenic forces continues to threaten the evolution and maintenance of biological diversity. This is of particular concern in tropical regions that are experiencing elevated rates of habitat loss. Although less well-studied than tropical rain forests, tropical dry forests (TDF) contain an enormous diversity of species and continue to be threatened by anthropogenic activities including grazing and agriculture. However, little is known about the processes that shape genetic connectivity in species inhabiting TDF ecosystems. We adopt a landscape genetic approach to understanding functional connectivity for leaf-toed geckos (Phyllodactylus tuberculosus) at multiple sites near the northernmost limit of this ecosystem at Alamos, Sonora, Mexico. Traditional analyses of population genetics are combined with multivariate GIS-based landscape analyses to test hypotheses on the potential drivers of spatial genetic variation. Moderate levels of within-population diversity and substantial levels of population differentiation are revealed by F _ST and D _est. Analyses using structure suggest the occurrence of from 2 to 9 genetic clusters depending on the model used. Landscape genetic analysis suggests that forest cover, stream connectivity, undisturbed habitat, slope, and minimum temperature of the coldest period explain more genetic variation than do simple Euclidean distances. Additional landscape genetic studies throughout TDF habitat are required to understand species-specific responses to landscape and climate change and to identify common drivers. We urge researchers interested in using multivariate distance methods to test for, and report, significant correlations among predictor matrices that can impact results, particularly when adopting least-cost path approaches. Further investigation into the use of information theoretic approaches for model selection is also warranted.