Recognition and cleavage of Biological Phosphates, Molecular Recognition, Mechanism and Biomedical Applications

01 July 2010 → 30 June 2015
European funding: framework programme
Research disciplines
  • Natural sciences
    • Organic chemistry
organic chemistry molecular design
Project description

Chemical Biology is a new, supradusciplinary field that unites the classically separate disciplines of Chemistry and biology. This network is centred around understanding the central biological process of phosphate transfer and combines leading experts in synthetic chemistry, enzyme model building, kinetic analysis, protein chemistry and directed evolution in a concerted effort to gain a quantitative understanding of transition states that are key to understanding how biological systems can achieve phosphate transfer with unrivalled efficiency. The quantitative language (i.e. kinetic and molecular recognition studies) used to describe and improve natural enzymes unites all participants and provides the theme for our training programme on analysis of phosphate transfer catalysis. Training in this area is highly interdisciplinary in nature requiring a joint effort of chemists and biologists centred around mechanistic thinking, which is at the core of this proposal. Ultimately our understanding of this central bioreaction should lead to useful applications on the long term, e.g. as artificial nucleases, with potential roles in gene regulation, if efficient catalysis can be combined with selective recognition. This proposal is part of a long-term strategy aimed at developing reagents which act by binding or catalytically (thus as artificial enzymes) to interfere with the expression of specific genes. This can be achieved through selective binding eventually (but not necessarily) followed by cleaving the nucleic acid backbone. Crucially for therapeutic success these reagents have to be delivered into the cell, which is why delivery issues are also addressed. The incorporation of industrial partners ensures that the full life-span of drug development is covered in this training programme.