Building proteins brick by brick

In situ click chemistry: from small molecule discovery to synthetic antibodiesScientists have become adept at synthesising novel nucleotide sequences from scratch, but our comparative lack of understanding of how proteins are built has hampered development of new proteins to use in the lab or as a therapy. Novel peptides have to be designed via a screening process rather than de novo synthesis and proteins which are produced in vivo, such as antibodies, can suffer from batch variation.

In this review, Steven Millward and colleagues from California and Singapore explore how the screening technology Iterative Peptide In Situ Click Chemistry (IPISC) could not only allow for greater control over the peptide synthesis process, but also increase the range and complexity of molecules we are able to produce.

The stepwise building method used in IPISC means that amino acids with particular properties, such as increased stability, can to added at the beginning of the process. This method also used target proteins as the scaffold on which to built, ensuring the the synthesised protein can bind effectively with its intended target. IPISC is also relatively easy to scale up from screening to full production when a suitable protein is identified.

This review doesn’t just cover the advantages of IPISC, but also discusses effective ways to analyse the results of a screen and areas where the method could be optimised further. To find out more, download the review here – it’s free for the next four weeks.

In situ click chemistry: from small molecule discovery to synthetic antibodies
Steven W. Millward, Heather D. Agnew, Bert Lai, Su Seong Lee, Jaehong Lim, Arundhati Nag, Suresh Pitram, Rosemary Rohde and James R. Heath
DOI: 10.1039/C2IB20110K

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