A new approach to synthesising polypeptide chains that works more like polythene manufacture than a biochemical reaction could lead to new materials, catalysts, and pharmaceuticals.

Huailin Sun and colleagues at Nankai University in China have used a raft of techniques including IR spectroscopy, MALDI-TOF mass spectrometry, and NMR spectroscopy, to track the synthesis and obtain structural identification of novel polypeptides constructed using a reaction akin to industrial olefin polymerisation. The team points out that this approach uses starting materials that are far less expensive than amino acids, the usual building blocks of polypeptides and proteins. They say it could make industrial production of novel compounds for a range of application.

Key to their success was the development of a catalyst that polymerises imine monomers, as opposed to amino acids, with an alternating carbon monoxide linker. The process emulates the well-known Ziegler-Natta approach to polymerization, which is based on an organometallic catalyst. The resulting structure formed from alternating reduced imine groups and the CO unit is identical to the amino acid chain of a conventionally produced polypeptide.

Ironically, for such a long-sought process, the team discovered that a simple acyl cobalt complex could polymerise imines with carbon monoxide. Cobalt salts are frequently used in carbonylation reactions, and so were the obvious choice to Sun and colleagues. They could then synthesize previously unknown polypeptides.
The researchers highlight the fact that the starting materials are readily available and inexpensive and that the reaction itself is the shortest abiotic route possible to polypeptides and "atom-economic". Such characteristics render the reaction well-suited to scale-up for production of synthetic polypeptides.
The next step will be to use a variety of imines as the monomers, rather than a single imine in each polypeptide chain, there are several problems to address. "To incorporate more than one type of imine into the polypeptide chain, for example, to obtain block copolymers, requires the reaction being a living polymerization," Sun told SpectroscopyNOW, "whereas, to control the insertion of monomers in a stepwise fashion will require the living end to be stable after each step of the insertion. These are the problems that we are going to solve."

Related links:

• Angew Chem, Int Edn, in press
• Nankai Chemistry

Article by David Bradley