CurlySMILES: a chemical language to customize and annotate encodings of molecular and nanodevice structures

CurlySMILES is a chemical line notation which extends SMILES with annotations for storage, retrieval and modeling of interlinked, coordinated, assembled and adsorbed molecules in supramolecular structures and nanodevices. Annotations are enclosed in curly braces and anchored to an atomic node or at the end of the molecular graph depending on the annotation type. CurlySMILES includes predefined annotations for stereogenicity, electron delocalization charges, extra-molecular interactions and connectivity, surface attachment, solutions, and crystal structures and allows extensions for domain-specific annotations. CurlySMILES provides a shorthand format to encode molecules with repetitive substructural parts or motifs such as monomer units in macromolecules and amino acids in peptide chains. CurlySMILES further accommodates special formats for non-molecular materials that are commonly denoted by composition of atoms or substructures rather than complete atom connectivity

Synthesis and Antiviral Evaluation of Carbocyclic Nucleoside Analogs of Nucleoside Reverse Transcriptase Translocation Inhibitor MK-8591 (4′-Ethynyl-2-fluoro-2′-deoxyadenosine)

MK-8591 (4′-ethynyl-2-fluoro-2′-deoxyadenosine) is a novel nucleoside analog that displays a differentiated mechanism of action as a nucleoside reverse transcriptase translocation inhibitor (NRTTI) compared to approved NRTIs. Herein, we describe our recent efforts to explore the impact of structural changes to the properties of MK-8591 through the synthesis and antiviral evaluation of carbocyclic derivatives. Synthesized analogs were evaluated for their antiviral activity, and the corresponding triphosphates were synthesized and evaluated in a biochemical assay. 4′-Ethynyl-G derivative (±)-29 displayed a promising IC50 of 33 nM in a hPBMC cell-based antiviral assay, and its triphosphate (TP), (±)-29-TP, displayed an IC50 of 324 nM in a biochemical RT-polymerase assay. Improved TP anabolite delivery resulting in improved in vitro potency was achieved by preparing the corresponding phosphoramidate prodrug of single enantiomer 29b, with 6-ethoxy G derivative 34b displaying a significantly improved IC50 of 3.0 nM, paving the way for new directions for this novel class of nucleoside analogs

[pt] AYLLUYACHIY: NOVO OLHAR SOBRE INCULTURAÇÃO E TEOLOGIA ÍNDIA

Revision control is a vital component of digital project management and has been widely deployed for text files. Binary files, on the other hand, have received relatively less attention. This can be in-convenient for graphics applications that use a significant amount of binary data, such as images, videos, meshes, and animations. Exist-ing strategies such as storing whole files for individual revisions or simple binary deltas could consume significant storage and obscure vital semantic information. We present a nonlinear revision con-trol system for images, designed with the common digital editing and sketching workflows in mind. We use DAG (directed acyclic graph) as the core structure, with DAG nodes representing editing operations and DAG edges the corresponding spatial, temporal and semantic relationships. We visualize our DAG in RevG (revision graph), which provides not only as a meaningful display of the re-vision history but also an intuitive interface for common revision control operations such as review, replay, diff, addition, branch-ing, merging, and conflict resolving. Beyond revision control, our system also facilitates artistic creation processes in common image editing and digital painting workflows. We have built a prototype system upon GIMP, an open source image editor, and demonstrate its effectiveness through formative user study and comparisons with alternative revision control systems

Synthesis and Antiviral Evaluation of Carbocyclic Nucleoside Analogs of Nucleoside Reverse Transcriptase Translocation Inhibitor MK-8591 (4′-Ethynyl-2-fluoro-2′-deoxyadenosine)

MK-8591 (4′-ethynyl-2-fluoro-2′-deoxyadenosine) is a novel nucleoside analog that displays a differentiated mechanism of action as a nucleoside reverse transcriptase translocation inhibitor (NRTTI) compared to approved NRTIs. Herein, we describe our recent efforts to explore the impact of structural changes to the properties of MK-8591 through the synthesis and antiviral evaluation of carbocyclic derivatives. Synthesized analogs were evaluated for their antiviral activity, and the corresponding triphosphates were synthesized and evaluated in a biochemical assay. 4′-Ethynyl-G derivative (±)-29 displayed a promising IC50 of 33 nM in a hPBMC cell-based antiviral assay, and its triphosphate (TP), (±)-29-TP, displayed an IC50 of 324 nM in a biochemical RT-polymerase assay. Improved TP anabolite delivery resulting in improved in vitro potency was achieved by preparing the corresponding phosphoramidate prodrug of single enantiomer 29b, with 6-ethoxy G derivative 34b displaying a significantly improved IC50 of 3.0 nM, paving the way for new directions for this novel class of nucleoside analogs