Lonza adds peptide tech to portfolio
technology that makes it possible to make peptide drugs that are
longer and have a more complex structure than is possible using
conventional techniques, reports Phil Taylor.
The technology, developed by German peptide development and production specialist AplaGen, should help Lonza tap the rich vein of peptide-based drugs coming through the research pipelines and onto the market.
AplaGen has developed a technique known as correctly-folded peptide synthesis (CFPS) that has a number of advantages over conventional approaches, according to Prof Hans-Georg Frank, one of the company's managing directors.
When peptides are manufactured, they are anchored to a solid phase and amino acids are added sequentially in a liquid phase to join to and create the growing peptide chain. Using conventional methods, the complete peptide chain is detached from its anchor and any modifications occur in solution.
The disadvantage of this is that the resulting peptides are loose in the liquid phase, and this can interfere with subsequent modifications to the molecule, for example folding it using disulphide bridges, that are required for its intended activity.
CFPS is based on a nickel based anchor which can allow detachment and re-attachment of the peptide chain after the end of synthesis. One immediate advantage is that this makes it much easier to purify using a process akin to affinity chromatography, boosting the yields that are achievable from the synthesis compared to conventional high-performance liquid chromatography of the liquid phase, said Prof Frank.
Another major advantage, he told In-Pharmatechnologist.com, is that modifications can not only be made to the molecule in the liquid phase, but also after it has been reattached to its anchorage. Once back in place, the peptide chains can be further modified whilst being held apart, minimising the risk of unwanted reactions that might occur should they be free to collide in solution.
The third advantage is that the technique can be used to join together peptide fragments, rather than individual amino acids, to make larger peptides than is currently possible, he said. This 'fragment condensation' approach is possible using current methods, but tends to be a very slow reaction and this increases the risk that the fragments join incorrectly (racemise) to make unwanted steroisomers.
Using CFPS, the fragments can be made in solution, which reduces the reaction time and the risk of racemisation, and then anchored to the solid phase to complete the synthesis.
This makes it possible to make larger peptides in the 20-60-mer range (i.e. 20-60 amino acids in length), said Prof Frank. At present, it is very difficult to make anything above 40-mer, he added.
At present, he estimates that there are several hundred peptide-based drugs in development, with the vanguard - such as Roche's novel HIV treatment Fuzeon (enfuvirtide) already on the market.
Last month, Lonza announced another technology agreement in its 'tides business, this time in the area of oligonucleotides - small nucleic acid sequences that form the basis of antisense and RNA interference products - another new class of drug that looks set to explode onto the marketplace in the next few years.
The collaboration with Belgium's RNA-TEC brings the companies the capability to offer both intermediate- and large-scale production capacities, allowing clients to take their projects from the preclinical stage right through to commercial production.
