Organic Synthesis Facility

Biography

Dr Marc Devocelle manages the Organic Synthesis Laboratory, which is part of the Centre for Synthesis and Chemical Biology and is located in the Royal College of Surgeons in Ireland

• Lecturer in the Department of Pharmaceutical & Medicinal Chemistry, RCSI (2004 to present)
• Manager of the HEA-funded Peptide Synthesis Laboratory at RCSI (2000 to present)
• HEA postdoctoral fellow in the Department of Chemistry at the Royal College of Surgeons in Ireland (1999)
• PhD in Organic Chemistry from the University of Lille (France), under contract with Sanofi (1997)

About the Organic Synthesis Laboratory

This facility is also one of the Core Technologies of the Programme for Human Genomics (PHG), established as a partnership between the Biopharmaceutical Sciences Network of the Royal College of Surgeons in Ireland (RCSI) and the Dublin Molecular Medicine Centre (DMMC). The laboratory is located in the Department of Pharmaceutical and Medicinal Chemistry at RCSI.

The Organic Synthesis Laboratory is dedicated to the solid phase synthesis and labelling of peptides and peptidomimetics.

Service

The mission statement of the laboratory is to provide an expertise in peptide chemistry and solid phase synthesis and to carry out the custom synthesis of chemical tools for life science research.

The laboratory has established several collaborations with Principal Investigators from the CSCB and the PHG. The services provided routinely include the synthesis of peptides (biotinylated, phosphorylated, lipophilic, fluorescently labelled, radiolabelled, homodetic, heterodetic and non-ribosomal) and peptidomimetics, used as chemical tools for the investigation of cell signalling pathways and lead discovery; the synthesis of peptide-based cell delivery systems and of biomolecule-peptide conjugates, used as prodrugs; the synthesis of chemical libraries for lead optimisation.

Intrumentation

The RCSI facility is equipped with two automated peptide synthesisers, one Applied Biosystems 433A and one parallel synthesiser (96 reactors) Advanced ChemTech 396W. One parallel (20 reactors) semi-automated organic synthesiser, Argonaut QUEST 210ASW, is used for the modification and labelling of the sequences assembled on the peptide synthesisers.

Organic Synthesis facility at RCSI, with a parallel peptide synthesizer (centre), an automated peptide synthesizer (right) and an automated HPLC system (left)

A fully automated HPLC PerSeptive Biosystems Biocad Sprint system, equipped with analytical and semi-preparative columns, autosampler and fraction collector, capable of running 100 individual analytical runs and collecting 100 fractions without supervision, is used for the analysis and purification of the macromolecules prepared.

Their characterisation is carried out in the Department of Clinical Pharmacology at RCSI, where three Mass Spectrometers (API 3000 Triple Quadrupole MS, Bruker Reflex III MALDI-TOF MS, Micromass QTOF MS) are available and in the Mass Spectrometry Facility at UCD.
Two freeze-dryers, Modulyo and Maxy-Dry-Lyo with vacuum concentrator, are used for the lyophilization of the final products.

Applications

Peptides exhibit a remarkable range of biological properties and can influence fundamental physiological processes with an unequalled potency and selectivity. They have therefore an important potential in medicine, not only as investigation tools in life science research, but also as drug candidates in their own right and finally for the production of prodrugs and drug delivery systems. Their clinical use may require their translation into peptidomimetics, non-peptide structures which retain the biological activity of the parent sequence.