Intranet
Acces
Contact
Publications
2008
Violette Aude, Lancelot Nathalie, Poschalko Alexander, Piotto Martial, Briand Jean-Paul, Raya Jesus, Elbayed Karim, Bianco Alberto, Guichard Gilles
Exploring helical folding of oligoureas during chain elongation by high-resolution magic-angle-spinning (HRMAS) NMR spectroscopy Article de journal
Dans: Chemistry (Weinheim an Der Bergstrasse, Germany), vol. 14, non 13, p. 3874–3882, 2008, ISSN: 0947-6539.
Résumé | Liens | BibTeX | Étiquettes: I2CT, Magnetic Resonance Spectroscopy, Molecular Structure, Solvents, Team-Bianco, Urea
@article{violette_exploring_2008,
title = {Exploring helical folding of oligoureas during chain elongation by high-resolution magic-angle-spinning (HRMAS) NMR spectroscopy},
author = {Aude Violette and Nathalie Lancelot and Alexander Poschalko and Martial Piotto and Jean-Paul Briand and Jesus Raya and Karim Elbayed and Alberto Bianco and Gilles Guichard},
doi = {10.1002/chem.200701923},
issn = {0947-6539},
year = {2008},
date = {2008-01-01},
journal = {Chemistry (Weinheim an Der Bergstrasse, Germany)},
volume = {14},
number = {13},
pages = {3874--3882},
abstract = {The development of novel folding oligomers (foldamers) for biological and biomedical applications requires both precise structural information and appropriate methods to detect folding propensity. However, the synthesis and the systematic conformational investigation of large arrays of oligomers to determine the influence of factors, such as chain length, side chains, and surrounding environment, on secondary structure can be quite tedious. Herein, we show for 2.5-helical N,N'-linked oligoureas (gamma-peptide lineage) that the whole process of foldamer characterization can be accelerated by using high-resolution magic-angle-spinning (HRMAS) NMR spectroscopy. This was achieved by monitoring a simple descriptor of conformational homogeneity (e.g., chemical shift difference between diastereotopic main chain CH2 protons) at different stages of oligourea chain growth on a solid support. HRMAS NMR experiments were conducted on two sets of oligoureas, ranging from dimer to hexamer, immobilized on DEUSS, a perdeuterated poly(oxyethylene)-based solid support swollen in solvents of low to high polarity. One evident advantage of the method is that only minute amount of material is required. In addition, the resonance of the deuterated resin is almost negligeable. On-bead NOESY spectra of high quality and with resolution comparable to that of liquid samples were obtained for longer oligomers, thus allowing detailed structural characterization.},
keywords = {I2CT, Magnetic Resonance Spectroscopy, Molecular Structure, Solvents, Team-Bianco, Urea},
pubstate = {published},
tppubtype = {article}
}
The development of novel folding oligomers (foldamers) for biological and biomedical applications requires both precise structural information and appropriate methods to detect folding propensity. However, the synthesis and the systematic conformational investigation of large arrays of oligomers to determine the influence of factors, such as chain length, side chains, and surrounding environment, on secondary structure can be quite tedious. Herein, we show for 2.5-helical N,N'-linked oligoureas (gamma-peptide lineage) that the whole process of foldamer characterization can be accelerated by using high-resolution magic-angle-spinning (HRMAS) NMR spectroscopy. This was achieved by monitoring a simple descriptor of conformational homogeneity (e.g., chemical shift difference between diastereotopic main chain CH2 protons) at different stages of oligourea chain growth on a solid support. HRMAS NMR experiments were conducted on two sets of oligoureas, ranging from dimer to hexamer, immobilized on DEUSS, a perdeuterated poly(oxyethylene)-based solid support swollen in solvents of low to high polarity. One evident advantage of the method is that only minute amount of material is required. In addition, the resonance of the deuterated resin is almost negligeable. On-bead NOESY spectra of high quality and with resolution comparable to that of liquid samples were obtained for longer oligomers, thus allowing detailed structural characterization.
2003
Green Clare, Brown Gemma, Dafforn Timothy R, Reichhart Jean-Marc, Morley Terri, Lomas David A, Gubb David
Drosophila necrotic mutations mirror disease-associated variants of human serpins Article de journal
Dans: Development, vol. 130, non 7, p. 1473–1478, 2003, ISSN: 0950-1991.
Résumé | BibTeX | Étiquettes: Animals, Humans, M3i, Necrosis, reichhart, Serpins, Temperature, Urea
@article{green_drosophila_2003,
title = {Drosophila necrotic mutations mirror disease-associated variants of human serpins},
author = {Clare Green and Gemma Brown and Timothy R Dafforn and Jean-Marc Reichhart and Terri Morley and David A Lomas and David Gubb},
issn = {0950-1991},
year = {2003},
date = {2003-04-01},
journal = {Development},
volume = {130},
number = {7},
pages = {1473--1478},
abstract = {Polymerization of members of the serpin superfamily underlies diseases as diverse as cirrhosis, angioedema, thrombosis and dementia. The Drosophila serpin Necrotic controls the innate immune response and is homologous to human alpha(1)-antitrypsin. We show that necrotic mutations that are identical to the Z-deficiency variant of alpha(1)-antitrypsin form urea-stable polymers in vivo. These necrotic mutations are temperature sensitive, which is in keeping with the temperature-dependent polymerization of serpins in vitro and the role of childhood fevers in exacerbating liver disease in Z alpha-antitrypsin deficiency. In addition, we identify two nec mutations homologous to an antithrombin point mutation that is responsible for neonatal thrombosis. Transgenic flies carrying an StextgreaterF amino-acid substitution equivalent to that found in Siiyama-variant antitrypsin (nec(StextgreaterF.UAS)) fail to complement nec-null mutations and demonstrate a dominant temperature-dependent inactivation of the wild-type nec allele. Taken together, these data establish Drosophila as a powerful system to study serpin polymerization in vivo.},
keywords = {Animals, Humans, M3i, Necrosis, reichhart, Serpins, Temperature, Urea},
pubstate = {published},
tppubtype = {article}
}
Polymerization of members of the serpin superfamily underlies diseases as diverse as cirrhosis, angioedema, thrombosis and dementia. The Drosophila serpin Necrotic controls the innate immune response and is homologous to human alpha(1)-antitrypsin. We show that necrotic mutations that are identical to the Z-deficiency variant of alpha(1)-antitrypsin form urea-stable polymers in vivo. These necrotic mutations are temperature sensitive, which is in keeping with the temperature-dependent polymerization of serpins in vitro and the role of childhood fevers in exacerbating liver disease in Z alpha-antitrypsin deficiency. In addition, we identify two nec mutations homologous to an antithrombin point mutation that is responsible for neonatal thrombosis. Transgenic flies carrying an StextgreaterF amino-acid substitution equivalent to that found in Siiyama-variant antitrypsin (nec(StextgreaterF.UAS)) fail to complement nec-null mutations and demonstrate a dominant temperature-dependent inactivation of the wild-type nec allele. Taken together, these data establish Drosophila as a powerful system to study serpin polymerization in vivo.
