The good, the bad and the twisted: a survey of ligand geometry in protein crystal structures

The protein databank now contains the structures of over 11,000 ligands bound to proteins. These structures are invaluable in applied areas such as structure-based drug design, but are also the substrate for understanding the energetics of intermolecular interactions with proteins. Despite their obvious importance, the careful analysis of ligands bound to protein structures lags behind the analysis of the protein structures themselves. We present an analysis of the geometry of ligands bound to proteins and highlight the role of small molecule crystal structures in enabling molecular modellers to critically evaluate a ligand model’s quality and investigate protein-induced strain

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Stereoelectronic control of addition reactions : the role played by an allylic substituent

The influence of an allylic substituent on the chemistry of the carbon carbon &pi; bond has been studied. Model compounds, with synclinal oxygen or carbon allylic substituents, have been sythesised. These include 5-methylene-2-phenyl-1,3-dioxane, 1-methylene-4-t-butylcyclohexane and E and Z 5,5'-di-t-butyl bis (1,3-dioxan-5-ylidene). Semi-empirical and ab initio computer calculations were carrried out for analogues of these compounds. The stereochemistry and regiochemistry exhibited by 5-methylene-1,3-dioxane, 1-methylene-4-t-butylcyclohexane and E and Z-5,5'-t-butyl bis (1,3-dioxanylidene), to electrophilic additions, was examined. Generally, methylene cyclohexane and methylene dioxane both exhibited endo (or axial) stereoselectivity with methylene dioxane showing greater specificity. Methylene cyclohexane exhibited Markownikoff regioselectivity whereas methylene dioxane surprisinly exhibited total anti-Markownikoff specificity. The calculations suggest that endo stereoselectivity is largely caused by hyperconjugation from the c_β/-x_γ/ bond with the HOMO. The greater endo selectivity exhibited by methylene dioxane is however, due to either exo bending of the double bond or, more likely, electrostatic considerations. It has been established that the observed regiochemistry in methylene dioxane is largely due to a hyperconjugative effect originating from the synclinal C-O bonds as the conformationally mobile model compound also studied, dimethoxy methylene propane, exhibits largely Markownikoff regiochemistry.</p

Libanius and Late Antique autobiography

Liebeschuetz John Hugo Wolfgang Gideon. Libanius and Late Antique autobiography. In: Topoi. Orient-Occident. Supplément 7, 2006. Mélanges A.F. Norman

E. Soler, Le sacré et le salut à Antioche, Beyrouth (2006)

Liebeschuetz J.W.G. E. Soler, Le sacré et le salut à Antioche, Beyrouth (2006) . In: Topoi, volume 15/2, 2007. pp. 791-797

Malalas on Antioch

Liebeschuetz John Hugo Wolfgang Gideon. Malalas on Antioch. In: Topoi. Orient-Occident. Supplément 5, 2004. Antioche de Syrie. Histoires, images et traces de la ville antique

Malalas on Antioch

Liebeschuetz John Hugo Wolfgang Gideon. Malalas on Antioch. In: Topoi. Orient-Occident. Supplément 5, 2004. Antioche de Syrie. Histoires, images et traces de la ville antique

E. Soler, Le sacré et le salut à Antioche, Beyrouth (2006)

Liebeschuetz J.W.G. E. Soler, Le sacré et le salut à Antioche, Beyrouth (2006) . In: Topoi, volume 15/2, 2007. pp. 791-797