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Synthesis of clusters containing lactose and their biological and structural evaluation


Dr. Sebastien Gouin, a French national who has completed his PhD is requesting funds for 1 year to work in Ireland with Dr. Paul V. Murphy to synthesise glycoclusters for biological evaluation. It is proposed that he will receive training in glycoconjugate synthesis and purification, NMR in determination of structure, mass spectrometry to study lectin clustering as well as gain exposure to other biological evaluations. This will diversify the expertise of the applicant who has worked previously on the synthesis of chelating agents for radioelements. Sebastien's PhD work provided a first approach to the principles of molecular design and chemical biology.

This consisted of the synthesis of radiopharmaceuticals, in particular of bifunctional chelating agents ( BCA). BCAs bearing aminocarboxylate functions, permit the complexation of radioelements and are suitable for nuclear medicine applications. The BCA also possess an active terminal allowing coupling to a specific biologic vector. Sebastien confirmed the complexation properties of his new ligands by labelling with different radioelements. Tests performed on the resulting complexes indicate that rigid and semi-rigid skeletons (pre-organization concept) are of considerable interest for the affinity of the radioelements. During the course of his PhD, completed at the University of Nantes (FR), the applicant gained experience in synthetic procedures and analytical techniques for investigation of the complexing abilities of new ligands.

Many fundamental aspects of in teraction of glycoclusters with lectins and the consequences of these interactions are not understood. Advances could lead to development of new tools for biology or drugs for medicine. Dr. Murphy's group in Dublin have developed restricted multivalent gly cosyl amide scaffolds for clustering receptors in solution and have published three papers to date on this topic.

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