Streamlining the manufacturing of biotherapeutics : SPPS vs. Recombinant protein production

Abstract: In this paper we have researched two methods for peptide synthesis; solid phase peptide synthesis (SPPS) and recombinant protein production, hereafter called recombinant production. The goal was to create a decision support that can be of use when choosing a production method for a given peptide. Additionally, we wanted to find a way to tell if a given sequence might be difficult to synthesize with SPPS, and in those cases recommend recombinant production as an alternative. To accomplish this, we have investigated general problems that may occur for the two methods as well as amino acid and sequence specific issues. We have also researched if there are any known solutions to avoid these problems, and by evaluating the gravity and frequency of the problems, with these solutions in mind, the decision support was created. A description of each considered issue is given, but the amount of each amino acid and the sequence of the amino acids in the peptide also needs to be considered when choosing the method. For 15 out of the 20 individual amino acids we have recommended the use of SPPS. For the remaining five, three are dependent on the placement within the sequence and in two cases we recommend considering recombinant production. We believe we have created a decision support that fulfills its purpose and can be of use when choosing the production method for future biotherapeutics.