Monitoring peptide synthesis

How to monitor peptide synthesis in SPPS with refractive index measurement

Peptides are becoming more and more present as they build the basis of many drugs on the current pharmaceutical and cosmetic market. Most peptides are synthesized using solid-phase peptide synthesis (SPPS) in smaller or larger scales. How can this process be monitored to control the process in real-time? The refractive index (RI) of a liquid provides key information about its physical properties and the composition of any solution. Recently papers were published showing that RI measurement is a process analytical tool (PAT) suitable for real-time monitoring of solid-phase peptide synthesis (SPPS). In SPPS protected amino acid derivates are successively added to a growing peptide chain that is immobilized on a solid phase. After adding the protected amino acid to the solid phase, it is deprotected and unreacted groups and side products are removed with washing steps. Afterwards the process is repeated to add further amino acids to the chain. Studies have proven that all these steps can be monitored in real-time by measuring the refractive index. As the refractive index varies in the function of the amount of mass dissolved in the liquid this tool can be used to monitor the solid-phase peptide synthesis in real-time. Solid-phase peptide synthesis can be carried out in smaller laboratory or larger production scales. Both processes can be monitored using Schmidt+Haensch refractometer. Smaller laboratory scale: To monitor the SPPS in small laboratory scales we recommend to use our VariRef laboratory refractometer. Together with a flow through sample compartment door and a membrane pump an at-line monitoring of small scale processes is possible. Larger production scale: To monitor SPPS in larger production scales we recommend to use the process refractometer IPR-FR2. This refractometer can either be used at-line or even in-line. Together with our bypass solution including bypass, hoses and rack it ensures a high quality process at-line monitoring of the SPPS process. However it can also be integrated directly into the pipeline or the production reactor.

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