Issue Date: January 26, 2009
Ralph F. Hirschmann Award In Peptide Chemistry
Sponsored by Merck Research Laboratories
Morten P. Meldal, a professor of chemistry at the Carlsberg Laboratory, in Valby, Denmark, is best known for his development of polyethylene glycol (PEG) resin-based systems and of copper(I)-catalyzed azide-alkyne cycloaddition click chemistry in peptide research. More broadly, he is recognized as a pioneer in fusing organic and combinatorial chemistry with peptide chemistry in the development of compound-screening technologies applicable to drug discovery.
Meldal, 55, earned a Ph.D. in chemical engineering, studying carbohydrate chemistry, from the Technical University of Denmark and did postdoctoral work with Robert C. Sheppard at Cambridge University. He has more than 300 publications to his credit and 23 patents in areas such as polymer-bead technology and methodologies for identifying compounds capable of modulating cellular responses.
Beginning with the development of techniques and instruments such as the carousel amino acid delivery system and real-time on-resin spectrophotometric monitoring, Meldal's career has been characterized by a series of inventions that allow real-time studies of solid-phase kinetics in peptide synthesis with the use of PEG resin bead substrates.
Meldal considers his work on click chemistry to be among his most practical innovations. He and K. Barry Sharpless, the professor of chemistry at Scripps Research Institute who originated the click concept of generating substances by joining small units together by chemoselective reactions, independently discovered the Cu(I) catalysis of the azide-alkyne Huisgen cycloaddition, which provides a quantitative ligation reaction at low temperature. "That has evolved into a sort of tool used by polymer chemists, biologists, and biochemists to 'click' together macromolecular architectures and attach things to surfaces," Meldal says.
Meldal's lab has had similar success developing peptide-based multiheterocyclic systems via a modification of the Pictet-Spengler reaction. "This gives us enormous diversity," Meldal says. "Its functionality incorporates reactive aldehydes into peptides, which allows the collapse of the peptides into cascade reactions, producing large heterocyclic systems. These reactions produce 'drugable' compounds."
In recent publications Meldal describes complexes of carbene-containing peptides with transition metals as a new type of stable, "green," solid-phase catalyst for highly efficient C–C bond formation.
The Carlsberg Laboratory, established by a large Danish brewery, is funded by the Danish National Research Foundation and is controlled by the Royal Danish Academy of Sciences & Letters. It is steeped in the practical application of science with an emphasis on patenting, and Meldal's laboratory continues to move new tools into industry. Novo Nordisk, for example, recently acquired rights to a fluorescent encoding technique patented by Meldal.
William D. Lubell, a professor of chemistry at the University of Montreal, who worked with Meldal while on sabbatical in 1999 and 2000, calls him "a tremendously creative person. He thinks things through very thoroughly and comes out with conceptual ideas—the whole idea of screening on resin, what is needed to do it, and how to identify hits." "Futuristic" is how Lubell characterizes the work Meldal has done in developing means of screening compounds produced through combinatorial chemistry.
Günther Jung, emeritus professor at the University of Tübingen, agrees. "He is a very organized researcher," says Jung, who has worked in the field of peptide chemistry and has known Meldal for 20 years. "He has been highly active in promoting science not only in his group but also in quite a number of workshops and symposia." Jung notes that Meldal's laboratory is highly international.
Going forward, Meldal says the key challenge in peptide chemistry will be to improve its fusion with organic chemistry in order to better exploit the diversity attained in both fields in a more coherent fashion in research. "Peptides are not just a tool," he says. "They are a means of getting compounds that are highly active and that can be made exactly the way you want them. It's happening already, but it needs to be done on a broader basis."
Meldal will present the award address before the Division of Organic Chemistry.
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