Juraj Bella | University of Edinburgh (original) (raw)

Papers by Juraj Bella

…, Jan 1, 1997

13 C NMR spectroscopy is the main source of information on the stereochemistry of Ziegler-Natta a... more 13 C NMR spectroscopy is the main source of information on the stereochemistry of Ziegler-Natta and related transition metal catalyzed propene polymerizations. In simple cases, like those of polypropylenes formed under pure enantiomorphic-site or chain-end control, the origin of the stereoselectivity can be easily recognized from the steric pentad distribution obtained from routine 13 C NMR spectra. On the other hand, the variety of innovative polymers that can now be prepared with "highyield" heterogeneous and metallocene-based homogeneous catalysts under hybrid, multiple, or oscillating stereocontrol represent very complex systems, which are beyond the possibilities of configurational analysis by routine 13 C NMR. In such cases, high-field 13 C NMR can be highly advantageous. Indeed, in this paper we show that from the methyl and methylene regions of 150 MHz 13 C NMR spectra of polypropylenes of various tacticities, the stereosequence distribution can be determined at a much finer level of detail, so as to obtain an adequate experimental basis for the investigation of the many complicated mechanisms of stereocontrol presently encountered in Ziegler-Natta catalysis.

…, Jan 1, 1998

We recently reported the assignment of the methyl and methylene regions in the 150 MHz 13 C NMR s... more We recently reported the assignment of the methyl and methylene regions in the 150 MHz 13 C NMR spectra of regioregular polypropylenes with different tacticities. In this article, we complete the assignment by extending it to the methine region. Despite a comparatively low ...

Journal of Inorganic Biochemistry

Chemical Science, 2010

Penetrative DNA intercalation and G-base selectivity of an organometallic tetrahydroanthracene Ru... more Penetrative DNA intercalation and G-base selectivity of an organometallic tetrahydroanthracene RuII anticancer complex.

Biomolecular NMR Assignments, 2009

The carboxy terminus of human complement component C7 comprises two Factor I-like Modules (FIMs) ... more The carboxy terminus of human complement component C7 comprises two Factor I-like Modules (FIMs) which are essential for formation of the Membrane Attack Complex, the terminal pathway of the innate immune system. C7-FIMs is a 16.9 kDa, recombinant, disulphide-rich, protein encompassing this C-terminal domain. Using conventional triple resonance experiments 93% of the (1)H, (15)N and (13)C assignment has been achieved, accounting for all assignment apart from a flexible N-terminus cloning artefact and an undefined loop. The chemical shifts have been deposited in the BioMagResBank; Accession No. 15996.

Biomolecular NMR Assignments, 2012

Human C7 is one of four homologous complement proteins that self-assemble on the nascent activati... more Human C7 is one of four homologous complement proteins that self-assemble on the nascent activation-specific fragment, C5b, thus forming the cytolytic membrane attack complex (MAC). In addition to the conserved modular core of the MAC/perforin protein family, C7 has four C-terminal domains comprising a pair of complement control protein modules (CCPs) preceding two Factor-I like modules (FIMs). It is proposed that the C7-CCPs might serve as a molecular arm for delivery of C7-FIMs to their binding site on C5b. Here we present the NMR chemical shift assignments for the C7-CCPs produced as a 14-kDa recombinant protein. Based upon triple-resonance experiments, 98 and 94 % of the backbone and side-chain ((1)H, (13)C and (15)N) assignments, respectively, have been completed. The chemical shifts and assignments have been deposited in the BioMagResBank database under accession number 18530.

Proceedings of the National Academy of Sciences, 2003

Organometallic chemistry offers novel concepts in structural diversity and molecular recognition ... more Organometallic chemistry offers novel concepts in structural diversity and molecular recognition that can be used in drug design. Here, we consider DNA recognition by 6 -arene Ru(II) anticancer complexes by an induced-fit mechanism. The stereochemistry of the dinuclear complex [(( 6 -biphenyl)RuCl(en)) 2 -(CH2)6] 2؉ (3, en ‫؍‬ ethylenediamine) was elucidated by studies of the half unit [( 6 -biphenyl)RuCl(Et-en)] ؉ (2, where Et-en is Et(H)NCH2CH2NH2). The structures of the separated R* RuR * N and S* RuR * N diastereomers of 2 were determined by x-ray crystallography; their slow interconversion in water (t1/2 Ϸ 2 h, 298 K, pH 6.2) was observed by NMR spectroscopy. For 2 and 3 the R* RuR * N configurations are more stable than S* RuR * N (73:27). X-ray and NMR studies showed that reactions of 2 and 3 with 9-ethylguanine gave rise selectively to S* RuR * N diastereomers. Dynamic chiral recognition of guanine can lead to high diastereoselectivity of DNA binding. The dinuclear complex 3 induced a large unwinding (31°) of plasmid DNA, twice that of mononuclear 2 (14°), and effectively inhibited DNA-directed RNA synthesis in vitro. This dinuclear complex gave rise to interstrand cross-links on a 213-bp plasmid fragment with efficiency similar to bifunctional cisplatin, and to 1,3-GG interstrand and 1,2-GG and 1,3-GTG intrastrand cross-links on site-specifically ruthenated 20-mers. Complex 3 blocked intercalation of ethidium considerably more than mononuclear 2. The concept of induced-fit recognition of DNA by organometallic complexes containing dynamic stereogenic centers via dynamic epimerization, intercalation, and cross-linking may be useful in the design of anticancer drugs.

Molecular Immunology, 2010

Complement receptor type 1 (CR1, CD35) is the erythrocyte's immune adherence receptor, vital for ... more Complement receptor type 1 (CR1, CD35) is the erythrocyte's immune adherence receptor, vital for clearance of C3b-and C4bopsonised particles. It also regulates alternative and classical complement pathways. Within its 30 CCP-module ectodomain, modules 1-3 comprise functional site 1 whilst two near-identical copies of site 2 occupy modules 8-10 and 15-17. Sites 1 and 2 have similar sequences but interact differentially with complement cascade proteins. Site 1 has a preference for C4b; site 2 prefers C3b. Moreover, site 1 preferentially mediates convertase decay acceleration whilst site 2 is more effective at factor I cofactor activity. The 3D structure of site 2 was solved previously but the structure of site 1 remains undetermined despite much effort. We have persisted with long-term efforts to solve the 3D structure of site 1. Expression of a codon-optimised gene in Pichia pastoris circumvented previous difficulties with protein yield. We prepared multiple-mg quantities of double-isotopically labelled (13C and 15N) samples of CR1 modules 1-2 (CR1 1-2) and CR1 1-3. The CR1 1-2 sample was employed to collect an extensive set of triple-resonance NMR spectra that were of sufficient quality to allow near-complete assignment of backbone and sidechain nuclei. Based on these assignments, distance restraints were extracted from nuclear Overhauser effect-spectra, which allowed a high-resolution 3D structure of CR1 1-2 to be calculated. This NMRderived structure and a newly refined, previously solved, structure of CR1 2-3 were supplemented by small-angle X-ray scattering data that helped to establish intermodular angles within the doublemodule constructs and within CR1 1-3, thus helping to morph the structures of CR1 1-2 and CR1 2-3 into a structure of site 1. Intermodular flexibility was characterised using NMR-based relaxation experiments. The new structure allows interpretation of previously performed homologous reverse-substitution experiments between sites 1 and 2.

Journal of Molecular Recognition, 2011

Jagged-1, one of the five Notch ligands in man, is a membrane-spanning protein made of a large ex... more Jagged-1, one of the five Notch ligands in man, is a membrane-spanning protein made of a large extracellular region and a 125-residue cytoplasmic tail bearing a C-terminal PDZ recognition motif ( 1213 RMEYIV 1218 ). Binding of Jagged-1 intracellular region to the PDZ domain of afadin, a protein located at cell-cell adherens junctions, couples Notch signaling with the adhesion system and the cytoskeleton. Using NMR chemical shift perturbation and surface plasmon resonance, we studied the interaction between the PDZ domain of afadin (AF6_PDZ) and a series of polypeptides comprising the PDZ-binding motif. Chemical shift mapping of AF6_PDZ upon binding of ligands of different length (6, 24, and 133 residues) showed that the interaction is strictly local and involves only the binding groove in the PDZ. The recombinant protein corresponding to the entire intracellular region of Jagged-1, J1_ic, is mainly disordered in solution, and chemical shift mapping of J1_ic in the presence of AF6_PDZ showed that binding is not coupled to folding. Binding studies on a series of 24-residue peptides phosphorylated at different positions showed that phosphorylation of the tyrosine at position -2 of the PDZ-binding motif decreases its affinity for AF6_PDZ, and may play a role in the modulation of this interaction. Finally, we show that the R1213Q mutation located in the PDZ-binding motif and associated with extrahepatic biliary atresia increases the affinity for AF6_PDZ, suggesting that this syndrome may arise from an imbalance in the coupling of Notch signaling to the cytoskeleton.

Journal of Magnetic Resonance, 2006

We have developed new 2D and 3D experiments for the measurement of C(alpha)-H(alpha) residual dip... more We have developed new 2D and 3D experiments for the measurement of C(alpha)-H(alpha) residual dipolar coupling constants in (13)C and (15)N labelled proteins. Two experiments, 2D (HNCO)-(J-CA)NH and 3D (HN)CO-(J-CA)NH, sample the C(alpha)-H(alpha) splitting by means of C(alpha) magnetization, while 2D (J-HACACO)NH and 3D J-HA(CACO)NH use H(alpha) magnetization to achieve a similar result. In the 2D experiments the coupling evolution is superimposed on the evolution of the (15)N chemical shifts and the IPAP principle is used to obtain (1)H-(15)N HSQC-like spectra from which the splitting is determined. The use of a third dimension in 3D experiments reduces spectral overlap to the point where use of an IPAP scheme may not be necessary. The length of the sampling interval in the J-dimension of these experiments is dictated solely by the relaxation properties of C(alpha) or H(alpha) nuclei. This was made possible by the use of C(alpha) selective pulses in combination with either a DPFGSE or modified BIRD pulses. Inclusion of these pulse sequence elements in the J-evolution periods removes unwanted spin-spin interactions. This allows prolonged sampling periods ( approximately 25 ms) yielding higher precision C(alpha)-H(alpha) splitting determination than is achievable with existing frequency based methods.

Journal of Inorganic Biochemistry, 2003

International Journal of Biological Macromolecules, 1996

An acidic exopolysaccharide was isolated from a selected strain of Aureobasidium pullulans. On th... more An acidic exopolysaccharide was isolated from a selected strain of Aureobasidium pullulans. On the basis of spectroscopic and chromatographic techniques, the polymer was identified as a beta-D-glucan containing a main chain of (1-->3)-linked beta-D-glucopy-ranosyl units substituted at the O-6 position by single beta-D-glucopyranosyl side chains. The ratio of units in the main chain to units in the side chain was found to be 1.4:1. The ionic character of this exopolysaccharide is due to the presence of malate residues which are linked to the polymer through ester bonds. The degree of substitution was estimated to be very low (0.05). In aqueous solution no signals are present in the NMR spectra strongly suggesting that the polymer adopts a rigid ordered conformation as further confirmed by rheological data. A solvent-induced conformational transition was observed in DMSO in which NMR spectra with good signal-to-noise ratio were obtained. The solution behaviour of the polymer is similar to that of other branched (1-->3)-beta-D-glucans in spite of both the degree of branching and the substitution with malate groups.

Structural Chemistry, 1998

... Giorgio Hamid Raza,1,3 Juraj Bella,1 Anna Laura Segre,1 Angelo Ferrando,2 and G. Goffredi2 ..... more ... Giorgio Hamid Raza,1,3 Juraj Bella,1 Anna Laura Segre,1 Angelo Ferrando,2 and G. Goffredi2 ... that two molecules of styrene react to form a 1,4-diradi-cal, which can evolve to produce a polymer or a by-product (1,2-diphenylcyclobutane, DPB), as confirmed by Pryor [2, 3 ...

Chemistry - A European Journal, 2006

Angewandte Chemie International Edition, 2006

Ruthenium(II) arene complexes of the type [(η 6 -arene)Ru(en)Cl] + (arene=eg p-cymene or biphenyl... more Ruthenium(II) arene complexes of the type [(η 6 -arene)Ru(en)Cl] + (arene=eg p-cymene or biphenyl; en=ethylenediamine) can exhibit anticancer activity in vitro and in vivo.1 They are pseudooctahedral, half-sandwich, piano-stool complexes with one reactive coordination ...

Synthetic Communications, 1993

ABSTRACT A direct synthesis of 3-aryl-3-substituted propionic esters and amides is described star... more ABSTRACT A direct synthesis of 3-aryl-3-substituted propionic esters and amides is described starting from Meldrum's acid, dimedone or 4-hydroxycoumarin and an aldehyde.