Project

Discipline

Inorganic Chemical Biology; Bioorganometallic Chemistry; Medicinal Inorganic Chemistry; Metal Complexes; Peptide Nucleic Acid (PNA); Caged Compounds; Metal Bioconjugates; Photo-release

Lead
Lay summary
Chemical Biology is the extraordinary endeavour of understanding, identifying and/or influencing biological processes in living cells using small molecules. Some metal-based compounds have been (and continue to be) selected to assist in this quest, for example, as anti-cancer agents, artificial proteases, artificial nucleases, artificial transporters of Ca2+, probes to demonstrate DNA charge transport, delivery vehicles for CO and NO, imaging agents, etc. All these biological applications employing metal complexes/organometallics have recently been referred to as Inorganic Chemical Biology.An important and useful strategy applied in Chemical Biology for the study of living organisms is the use of light-responsive caged compounds. In these studies, biologically relevant molecules (glutamates, proteins, nucleic acids, etc…), rendered inactive by a photolabile protecting group (PLPG), were introduced into living cells/organisms. Upon activation of light, the irreversible release of these biologically active molecules at a specific time and location could be achieved. Despite great success observed in these such studies, the examples of released metal complexes for biological purposes are currently non-existent.With this in mind, in this proposal, I present a general concept to specifically release metal complexes of biological/medicinal relevance from metal-containing bioconjugates using light as an external trigger. Biologically specific cellular transporters/recognition units will be coupled, using different synthetic methods to photoremovable protecting groups, to which metal complexes with different properties will be attached. Upon light activation, the metal complexes will be liberated and will therefore be able to undertake a specific function within the cell.The general outcome from this cross-disciplinary research will be of significant interest in various areas such as inorganic chemistry, bioorganometallic chemistry, medicinal chemistry, biochemistry and biophysical chemistry.

Direct link to Lay Summary

Last update: 21.02.2013

Title	Year

Number	Title	Start	Funding scheme

In this proposal, I present a general concept to specifically release metal complexes of biological/medicinal relevance from metal-containing bioconjugates using light as an external trigger. Biologically specific cellular transporters/recognition units (peptides, proteins, nucleic acids, peptide nucleic acids (PNAs), biotin, (poly)saccharides, hormones, lipids, etc…) will be coupled, using different synthetic methods (native chemical ligation, peptide coupling, click chemistry, etc...), to photoremovable protecting groups, to which metal complexes with different properties will be attached. Upon light activation, the metal complexes will be liberated and will therefore be able to undertake a specific function within the cell (cytotoxicity, imaging, enzyme inhibition, DNA/RNA/protein cleavage, etc…).