Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• cavities that could be filled to enhance protein stability. When these cavities were filled by genetic mutagenesis of the SOD1 protein, enhanced dimer stability was detected [36]. An in silico screen was performed to identify compounds with the potential to bind at the dimer interface and the top 100 hits

• protein aggregation. Top: selected compounds identified in high-throughput screening. Bottom: advanced compounds. Compounds identified by Nowak and co-workers [37] in silico that selectively bind SOD1 over human plasma and inhibit A4V-SOD1 aggregation

Exploring chemical diversity via a modular reaction pairing strategy

• Joanna K. Loh,
• Sun Young Yoon,
• Thiwanka B. Samarakoon,
• Alan Rolfe,
• Patrick Porubsky,
• Benjamin Neuenswander,
• Gerald H. Lushington and
• Paul R. Hanson

Beilstein J. Org. Chem. 2012, 8, 1293–1302, doi:10.3762/bjoc.8.147

• identical conditions, thus attempts were not made to optimize the conditions further for individual substrates. Library design An 80-member, full matrix library was designed by using in silico analysis [38]. Eight benzoxathiazocine 1,1-dioxide scaffolds 1–8 were designed, of which library I (1–4) was

• products with undesirable in silico properties (see Supporting Information File 1 for full in silico data and detailed information on the calculations). These metric filters included standard Lipinski’s rule of five parameters (molecular weight <500, ClogP <5.0, number of H-acceptors <10, and number of H

• both libraries I and II demonstrated that the primary objectives set out in the library design were achieved; final masses ranged between 18–127 mg and the average final mass was 68 mg (original target being 50 mg). In silico analysis of chemical diversity and drug-likeness In silico analysis of the

Synthesis and in silico screening of a library of β-carboline-containing compounds

• Kay M. Brummond,
• John R. Goodell,
• Matthew G. LaPorte,
• Lirong Wang and
• Xiang-Qun Xie

Beilstein J. Org. Chem. 2012, 8, 1048–1058, doi:10.3762/bjoc.8.117

• NIH Molecular Repository (MLSMR) and may target proteins such as histone deacetylase 4, endothelial nitric oxide synthase, 5-hydroxytryptamine receptor 6 and mitogen-activated protein kinase 1. These in silico screening results aim to add value to the β-carboline library of compounds for those

• interested in probes of these targets. Keywords: β-carboline; biological activity; chemical diversity; diversity-oriented synthesis; in silico screening; Introduction Identification of a comprehensive set of small organic molecules capable of selectively modifying the function of biological targets

• maximally diverse chemical space. The synthesis of a modified subset of this virtual compound library is described within, where modifications were mainly driven by studies of compound stability. Furthermore, a high throughput, in silico screening analysis of this library identified a number of potential

The use of glycoinformatics in glycochemistry

• Thomas Lütteke

Beilstein J. Org. Chem. 2012, 8, 915–929, doi:10.3762/bjoc.8.104

• used to create models of carbohydrate chains. The latter program can also perform in silico glycosylation by adding the glycan chains to a protein 3D structure, and provides input files for the AMBER [94][95] modeling programs using the GLYCAM force field [99]. Glycan 3D structures calculated by Sweet

• peaks that are observed in a spectrum are compared to theoretically derived fragment masses that are computed from glycan structures stored in a carbohydrate database. This approach, however, is limited by the content of the database that provides the templates for in silico fragmentation, which means

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• {[(β-D-galactopyranosyl)oxy]methyl}furan (BGF) nor methyl β-D-galactopyranoside nor 3,4-bis(hydroxymethyl)furan, which were used as controls, eliciting comparable biological activity. In silico modeling experiments, in which binding of GSF to the extracellular domain of the integrin αvβ3 was determined

• (hydroxymethyl)furan and benzoylated galactose imidate, is nontoxic and antagonizes cell physiological processes in vitro that are important for the dissemination and growth of tumor cells in vivo. Keywords: angiogenesis; biomimetic synthesis; carbohydrates; in silico blind docking; melanoma cells

• [25] created a β-D-mannose-containing inhibitor of α4β1 based on in silico modeled structures. In silico analysis of GSF interaction with integrins Our data showing similar inhibition of melanoma cell attachment to fibronectin by GSF as by the combined integrin ligand peptides, also points to an