Picking natural peptides.(Computational chemistry)

A promising class of pharmaceutically active natural products, extracted from algae and bacteria, known as non-ribosomal peptides (NRPs), could be sped through the patenting process faster thanks to some clever computational chemistry. NRPs represent a potentially huge repository of bioactive compounds with powerful drugs, such as penicillin, belonging to this family.

The researchers from the University of California, San Diego, US, concentrated their efforts on developing a technique that would allow researchers looking for medically useful cyclic NRPs to discover if other research groups had already found these compounds. To do this, they used mass spectrometry to break the peptides up into fragments and used computer algorithms to stitch together, and uncover, their structure. They then created 'dereplication' tools to ensure that the compound was novel and had not already been patented.

This involved taking a database of known NRP chemical structures and computing virtual mass spec signals, which were then compared to the NRP of interest (Nature Methods doi:10.1038/nmeth.1350).

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NRPs are produced by bacteria and other microorganisms, usually as a defence against other microorganisms. NRPs are not coded for in the organism's DNA and are synthesised by enzymes out of a wide range of amino acids, rather than the 20 usually associated with protein production. Author Julio Ng says that some NRP databases have more than 500 of these building blocks, meaning that there are a potentially huge number of these compounds out there.

Marshall Bern, a computational geometry researcher at Palo Alto Research Center in the US, says that this is an 'important paper.... A cheap assay that can associate an unknown compound with related previously studied compounds could save a lot of time and money.' However, one problem with this approach, Bern adds, is that NRP databases are currently rather limited in their scope.

The system currently only works with cyclic peptides, but Ng says that the plan is to extend this to linear and cyclic peptides with a tail. The researchers have filed a patent on their idea, but will make it freely available to the academic community.

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