5 August 2005: Therapeutic potential grows on trees

Researchers in The Netherlands say they have developed a uniquely versatile method for stitching whole proteins and peptides onto dendrimer molecules. The tree-like structures have vast potential as therapeutic and diagnostic agents, said Bert Meijer, professor of molecular sciences at the Eindhoven University of Technology, who led the work.

The method differs from previous versions where individual amino-acids were added step-by-step. In Meijer’s protocol, the dendrimer is initially ’dressed’ with cysteine residues, a key step to ensuring controlled addition. These residues are then coupled to proteins and oligopeptides bearing thioester groups in a process called Native Chemical Ligation. Precise control of the reaction conditions leads to well-defined dendrimer-protein hybrids that are characterised using electrospray mass spectroscopy. 

Meijer says the scheme is highly flexible, creating single molecules with multiple layers of functionality for a variety of imaging and binding applications.   ’The prospects are enormous,’ he said.   

Jean-Louis Reymond, professor of chemistry and biochemistry at the University of Berne, Switzerland, who also works in this area, warns of several drawbacks to Meijer’s technique. The main disadvantage, he said, is that the traditional amino-acid route is easier to control synthetically.  

But Reymond acknowledges that Meijer’s approach has the advantage that proteins and peptides are attached directly, thereby accessing a different set of architectures.   ’Native chemical ligation is a very practical way to stitch pieces together.   I think it’s very exciting and has lots of applications,’ he said.  Gaetano Mancino