Bypassing the ribosome: peptide synthesis without translation.

Chemical peptide synthesis is well-established but has drawbacks, notably the need to protect side-chain functional groups during reactions. Proteolytic enzymes may be used 'in reverse' to catalyse peptide synthesis without side-chain protection and avoiding the danger of racemization. Enzymic syntheses may use either an equilibrium or a kinetic strategy. Equilibrium synthesis is simply the reversal of hydrolysis, using any type of protease. Kinetic synthesis involves time-dependent acyl transfer using activated substrates and a serine or cysteine protease. Enzymic synthesis often takes place in partially aqueous or non-aqueous reaction media; the medium can often desirably influence the protease's properties. It is possible to tailor a protease to improve its usefulness in peptide synthesis; one can alter the enzyme's properties by means such as chemical modification, PEG-coupling or protein engineering.