Institute for Pharmaceutical science
Institute for Pharmaceutical science
Longo J.,French National Center for Scientific Research |
Yao C.,Albert Ludwigs University of Freiburg |
Rios C.,French National Center for Scientific Research |
Chau N.T.T.,French National Center for Scientific Research |
And 8 more authors.
Chemical Communications | Year: 2015
GFP has been genetically modified at two specific positions of its molecular architecture. These modifications allow its covalent attachment onto PEG brushes grafted on functionalized silicone surfaces. The stretching of this material leads to a reversible decrease of the fluorescence intensity due to stretch-induced forces applying on GFP molecules. This journal is © The Royal Society of Chemistry 2015.
Pagano B.,King's College London |
Pagano B.,University of Naples Federico II |
Jama A.,Institute for Pharmaceutical Science |
Martinez P.,King's College London |
And 5 more authors.
PLoS ONE | Year: 2013
The p53 family of genes and their protein products, namely, p53, p63 and p73, have over one billion years of evolutionary history. Advances in computational biology and genomics are enabling studies of the complexities of the molecular evolution of p53 protein family to decipher the underpinnings of key biological conditions spanning from cancer through to various metabolic and developmental disorders and facilitate the design of personalised medicines. However, a complete understanding of the inherent nature of the thermodynamic and structural stability of the p53 protein family is still lacking. This is due, to a degree, to the lack of comprehensive structural information for a large number of homologous proteins and to an incomplete knowledge of the intrinsic factors responsible for their stability and how these might influence function. Here we investigate the thermal stability, secondary structure and folding properties of the DNA-binding domains (DBDs) of a range of proteins from the p53 family using biophysical methods. While the N- and the C-terminal domains of the p53 family show sequence diversity and are normally targets for post-translational modifications and alternative splicing, the central DBD is highly conserved. Together with data obtained from Molecular Dynamics simulations in solution and with structure based homology modelling, our results provide further insights into the molecular properties of evolutionary related p53 proteins. We identify some marked structural differences within the p53 family, which could account for the divergence in biological functions as well as the subtleties manifested in the oligomerization properties of this family. © 2013 Pagano et al.
Kraljevic T.G.,University of Zagreb |
Kristafor S.,University of Zagreb |
Suman L.,Ruder Boskovic Institute |
Kralj M.,Ruder Boskovic Institute |
And 3 more authors.
Bioorganic and Medicinal Chemistry | Year: 2010
5,6-Disubstituted pyrimidine derivatives (3-20) were prepared by intramolecular cyclization reaction of α-(1-carbamyliminomethylene)-γ-butyrolactone (2) with sodium ethoxide and subsequent chemical transformation of 2-hydroxy group in C-5 side chain as well as lithiation reaction for introduction of acyclic side chain at C-6. All compounds were characterized by 1H NMR, 13C NMR and mass spectra. Structures of compounds 4, 7 and 14 were unambiguously confirmed by X-ray crystal structural analysis. Supramolecular structures of these three compounds differ significantly. Two N-H⋯O and one C-H⋯O hydrogen bonds in 4 form three-dimensional network. One O-H⋯N hydrogen bond and one π⋯π interaction self-assemble the molecules of 7 into sheets. In supramolecular aggregation of 14, only π⋯π stacking interactions participate, so forming chains. The compounds were evaluated for their cytostatic activities against human malignant cell lines. Of all tested compounds, 2,4-dimethoxy-5-methoxytritylethylpyrimidine (9) and 2,4-dichloro-5-chloroethylpyrimidine (14) exhibited the most prominent inhibitory effects. Furthermore, compound 14 showed marked activity against human colon carcinoma (IC50 = 0.4 μM). © 2010 Elsevier Ltd. All rights reserved.
Stefansdottir G.,University Utrecht |
Stefansdottir G.,Institute for Pharmaceutical science |
Zoungas S.,University of Sydney |
Zoungas S.,Monash University |
And 10 more authors.
Diabetologia | Year: 2011
Aims/hypothesis: Type 2 diabetes has been associated with an increased risk of cancer. This study examines the effect of more vs less intensive glucose control on the risk of cancer in patients with type 2 diabetes. Methods: All 11,140 participants from the Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) trial (ClinicalTrials.gov NCT00145925) were studied. Cancer incidence and cancer mortality was compared in groups randomised to intensive or standard glucose control. Information on events during follow-up was obtained from serious adverse event reports and death certificates. HRs (95% CI) were calculated for all cancers, all solid cancers, cancer deaths and site-specific cancers. Results: After a median follow-up of 5 years, 363 and 337 cancer events were reported in the intensive and standard control groups, respectively (incidence 1.39/100 person-years [PY] and 1.28/100 PY; HR 1.08 [95% CI 0.93-1.26]). The incidences of all solid cancers and cancer deaths were 1.25/100 PY and 0.15/100 PY in the intensive group and 1.15/100 PY and 0.13/100 PY in the standard group (HR 1.09 [95% CI 0.93-1.27] for solid cancers, and 1.17 [0.75-1.84] for cancer death). Across all the major organ systems studied, no significant differences in the cancer incidences were observed in the intensive and standard control groups. Conclusions/interpretations: More intensive glucose control achieved with a regimen that included greater use of gliclazide, insulin, metformin and other agents, did not affect the risk of cancer events or death in patients with type 2 diabetes. © 2011 Springer-Verlag.