Polyalanine expansions in transcription factors have been associated with eight distinct congenital human diseases. It is thought that in each case the polyalanine expansion causes misfolding of the protein that abrogates protein function. Misfolded proteins form aggregates when expressed in vitro; however, it is less clear whether aggregation is of relevance to these diseases in vivo. To inves...

Although the program SHELXE was originally intended for the experimental phasing of macromolecules, it can also prove useful for expanding a small protein fragment to an almost complete polyalanine trace of the structure, given a favourable combination of native data resolution (better than about 2.1 Å) and solvent content. A correlation coefficient (CC) of more than 25% between the native stru...

Polyalanine derivatives containing cysteamine linker R-(Ala)14NH-(CH2)2-SH, where R is ferrocenecarbonyl or hydrogen, were synthesized and then used to form self-assembled monolayers on gold. The tilt angles and the packing density of the molecules within monolayer assemblies were determined by FTIR spectroscopy and scanning tunneling microscopy, respectively. Electrochemical properties of mono...

The effect of a solvation on the thermodynamics and kinetics of polyalanine (Ala(12)) is explored on the basis of its energy landscapes in vacuum and in an aqueous solution. Both energy landscapes are characterized by two basins, one associated with alpha-helical structures and the other with coil and beta-structures of the peptide. In both environments, the basin that corresponds to the alpha-...

To the Editor : Synpolydactyly (SPD; MIM 186000) is a rare autosomal dominant limb deformity, with a distinctive combination of syndactyly and polydactyly. The main features of SPD are the webbing of the Third or Fourth fingers and Fourth or Fifth toes, with partial or complete digital duplication within the syndactylous web (1, 2). Currently, SPD is classified into three types, SPD1–SPD3. Of t...

OPMD Therapy Progress 2 ARC Publishing Introduction Oculopharyngeal muscular dystrophy (OPMD) is a midlife onset (~45 years) primarily autosomal dominant muscular disease with minor neuronal involvement [1]. It is characterized by progressive swallowing difficulties, eyelid drooping and serious proximal limb weakness at later stages. The pathological hallmark of the disease is the presence of i...

The analytic energy gradients for the combined fragment molecular orbital and polarizable continuum model (FMO/PCM) method are derived and implemented. Applications of FMO/PCM geometry optimization to polyalanine show that the structures obtained with the FMO/PCM method are very close to those obtained with the corresponding full ab initio PCM methods. FMO/PCM (RHF/6-31G* level) is used to opti...

X-ray diffraction studies of a D-galactose-binding protein essential for transport and chemotaxis in Escherichia coli have yielded a model of the polypeptide chain backbone. An initial polyalanine backbone trace was obtained at 3.2 A resolution by the molecular replacement technique, using a polyalanine search model derived from the refined structure of the L-arabinose-binding protein. Concurre...

The synthesis of well-defined homo- and co-polypeptides L-alanine (L-Ala) by ring-opening polymerization (ROP) its N-carboxyanhydride (NCAs), either via suspension/interfacial- or solution phase-polymerization using 10-undecene-1-amine ?,?-diamino poly(ethylene glycol) (8 1.5 kDa) as primary amine initiators is reported. When conducting ROP NCA-alanine under suspension/interfacial conditions, b...