Solid Phase Phospholipid and Dendrimer Synthesis (SOPHOLIDES)
Introduction of solid-phase organic synthesis will reinforce the IOPC's capabilities in the field of lead optimisation and discovery. The large number of emerging targets, which are expected from functional genomics, demands novel and effective approaches for the hit and lead generation process as well as the lead optimisation phase. Concerning ether phospholipid research at IOPC, generation of focused libraries of ether phospholipids containing designed elements of diversity will have a significant input on the faster development of potential drug candidates. Several structural analogues can be followed simultaneously which should result in faster development times and thus effectively help to reduce overall development costs. The knowledge that will be transferred by the incoming researcher will also be of overall benefit IOPC since SPOS could be introduced in all the ongoing research projects of the pharmaceutical chemistry group and also to the other research directions of IOPC. The development of dendrimer chemistry will also promote the research profile of the IOPC in a rapidly expanding area with many potential commercial applications. The applications of dendrimers extend far beyond those presented in the proposed project and will benefit many of the other activities of the IOPC, especially those in the fields of catalysis and functional materials. The aim is to eventually develop a high level expertise, making the IOPC a focal point for this activity in Greece. The third facet of this proposal involves applications of high-energy techniques. These, too have potential and proven applications in many areas outside of organic synthesis and the transfer of knowledge in the use of these techniques to the IOPC will in turn eventually place it in a position to be able to provide the requisite knowledge to other institutes and organisations in Greece interested in their applications. All the capabilities which will arise form the knowledge transfer within the framework of this programme will place IOPC in a privileged position with respect to other Greek Research Centres and Universities involved in chemistry research.
More specifically the objectives of ''Sopholides'' are the following:
Development of solid phase methods for dendrimer synthesis. In the context of "Sopholides" these materials will be used to produce modified resins.
Development of dendrimer-modified resins for solid phase synthesis with the objective of increasing the loading capacity of the conventionally used resins.
Development of cost effective, reliable and efficient technologies based on solid phase for the generation of bioactive phospholipids. These should be amenable to the introduction of designed elements of diversity leading to the synthesis of EP's and phosphonolipids.
Application of high-energy microwave and ultrasound techniques. These techniques have a proven applicability in SPOS.
Generation of focused libraries of reduced size of ether phospholipids and phosphonolipids with the aim of optimisation of structural features of lead compounds for specific biological applications including antiprotozoal therapeutics and anticancer compounds.
Increasing the competitiveness of a European research facility situated in a less favoured region by introducing SPOS as a tool for lead optimisation and discovery and by developing its expertise in dendrimer chemistry.
Training of young researchers in modern techniques with important applications in chemistry, providing them with training in a) modern technologies and skills highly valued in the EU chemical and pharmaceutical industry, and b) collection and analysis of the data for structure activity relationship studies.
Dissemination of results to the scientific, industrial and general public; conference presentations, publications in scientific journals, public relations, project homepage; eventual patenting; systematic investigation of industrial applications of results.
İ National Hellenic
Research Foundation (NHRF), 48 Vassileos Constantinou Ave., 11635 Athens,
Greece, Tel. +302107273700, Fax. +302107246618