Chemistry and Modelling for Protein Recognition

Team Publications

Year of publication 2008

François Besselièvre, Florence Mahuteau-Betzer, David S Grierson, Sandrine Piguel (2008 Mar 20)

Ligandless microwave-assisted Pd/Cu-catalyzed direct arylation of oxazoles

The Journal of organic chemistry : 3278-3280 : DOI : 10.1021/jo7027135 Learn more

An efficient microwave-assisted palladium/copper co-mediated direct arylation of oxazoles with aryl bromides under ligandless conditions has been developed. The method is functional group tolerant and provides rapid access to medicinally relevant compounds in good yields. Coupled to the van Leusen oxazole ring synthesis, this methodology is illustrated by an expedient two-step synthesis of the four 2,5-diaryloxazole alkaloids texamine, texaline, balsoxin, and O-Me-halfordinol from commercially available starting materials.

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Year of publication 2005

A Dupuy, A Shamsaldin, E Quiniou, C Paoletti, M Labbé, M F Avril, D Lefkopoulos, F de Vathaire (2005 Oct 26)

Risk of melanoma following adulthood cancer: a case-control study.

European journal of cancer (Oxford, England : 1990) : 41 : 2904-2910 : DOI : 10.1016/j.ejca.2005.07.020 Learn more

Melanoma is a severe skin cancer related to sun exposure. Whether this malignancy is linked to exposure to ionising radiation during adulthood is still controversial. This case-control study examined the risk of melanoma following treatment for an adulthood first malignant neoplasm (FMN). Cases were patients who presented with cutaneous melanoma after a first cancer in adulthood. Controls (3 per case) were patients free of melanoma, matched for age, duration of follow-up since the FMN, type of FMN, and followed in the same institution. A total of 57 cases and 171 controls were included. In the final multivariate analysis, no risk of melanoma was associated with radiotherapy (odds ratio (OR) for 1 Gy = 1.01, 95% confidence interval (95%CI) 0.96-1.07) nor hormonotherapy, whereas chemotherapy use (OR = 2.3, 95%CI 0.93-5.6) and having a history of familial cancer (OR = 2.8, 95%CI 1.3-5.9) exhibited a nearly significant risk. In conclusion, unlike the evidence for risk of exposure to ionising radiation during childhood, we did not substantiate a risk for association of melanoma with exposure to ionising radiation during adulthood. The risk associated with chemotherapy should justify the implementation of skin surveillance for early detection of melanoma in these patients.

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Year of publication 2003

Catherine Tetreau, Yves Blouquit, Eugene Novikov, Eric Quiniou, Daniel Lavalette (2003 Dec 26)

Competition with xenon elicits ligand migration and escape pathways in myoglobin.

Biophysical journal : 86 : 435-447 : DOI : 10.1016/S0006-3495(04)74120-X Learn more

Evidence for ligand migration toward the xenon-binding cavities in myoglobin comes from a number of laser photolysis studies of MbO2 including mutants and from cryo- and time-resolved crystallography of MbCO. To explore ligand migration in greater detail, we investigated the rebinding kinetics of both MbO2 and MbCO under a xenon partial pressure ranging from 1 to 16 atm over the temperature range (293-77 K). Below 180 K xenon affects to a significant, but minor, extent the thermodynamic parameters for rebinding from the primary docking site in each Mb taxonomic substate. Above 200 K the ligand migrates to the proximal Xe1 site but when the latter is occupied by xenon a new kinetic process appears. It is attributed to rebinding from transient docking sites located on the path between the primary and the secondary docking site of both ligands. Ligand escape exhibits a more complicated pattern than expected. At room temperature O2 and CO escape appears to take place exclusively from the primary site. In contrast, at T approximately 250 K, roughly 50% of the CO molecules that have escaped from the protein originate from the Xe1 secondary site.

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S Guérin, A Dupuy, H Anderson, A Shamsaldin, G Svahn-Tapper, T Moller, E Quiniou, S Garwicz, M Hawkins, M F Avril, O Oberlin, J Chavaudra, F de Vathaire (2003 Oct 15)

Radiation dose as a risk factor for malignant melanoma following childhood cancer.

European journal of cancer (Oxford, England : 1990) : 39 : 2379-86 : DOI : 10.1016/S0959-8049(03)00663-4 Learn more

The aim of this study was to determine therapy-related risk factors for the development of melanoma after childhood cancer. Among 4401 3-year survivors of a childhood cancer in eight French and British centres and 25120 patients younger than 20 years old at first malignant neoplasm (FMN) extracted from the Nordic Cancer Registries, 16 patients developed a melanoma as a second malignant neoplasm (SMN). A cohort study of the French and British cohorts was performed. In a nested case-control study, the 16 patients who developed a melanoma as a SMN (cases) were matched with 3-5 controls in their respective cohort according to gender, age at the first cancer, the calendar year of occurrence of the first cancer and follow-up. Radiotherapy appeared to increase the risk of melanoma for local doses >15 Gy, Odds Ratio (OR)=13 (95% Confidence Interval (CI): 0.94-174). Regarding chemotherapy, we observed an increased OR for both alkylating agents and spindle inhibitors, OR=2.7 (95% CI: 0.5-14). Children treated for a gonadal tumour as a FMN were found to be at a higher risk of melanoma, OR=8.7 (95% CI: 0.9-86). The adjusted OR for the local radiation dose was 1.07 (95% CI: 1.00-1.15). In conclusion, radiotherapy may contribute to an increased risk of melanoma as a SMN, but only at very high doses of low linear energy transfer radiation. Common genetic origins between gonadal tumours and malignant melanomas are likely.

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