Peptide-based research tools are a valuable asset in performing basic biological research. The availability of for consistent, high quality reagents is a vital element in the researcher’s toolbox in order to study areas such as receptor binding, and cell biology.
Total chemical synthesis offers the researcher a high degree of control in the design of standard and bespoke peptide-based research tools. The nature of solid phase peptide synthesis (SPPS) allows the incorporation of natural or unnatural modifications in a highly specific manner leading to reproducible manufacturing methods and product quality. Historically, SPPS methods limited the length of peptides that could be produced chemically to 40-60 amino acids, but modern methods have now pushed the boundary beyond 100 amino acids enabling small proteins to become legitimate targets for synthesis.
Almac has developed methods in SPPS in the development of relevant peptide / small protein targets such as chemokines (70-80 amino acids), ubiquitin reagents (76 amino acids), and histones (ca. 135 amino acids). Historically, recombinant methods of production have been able to cope with the sheer length of the sequences, but been nor been able to control the introduction of site-specific modifications, such as fluorophores, or post-translational modifications such as methylations or phosphorylations. Almac has perfected methods of synthesis of such challenging molecules to produce physiologically relevant reagents that previously were not obtainable.
In this paper, we describe the synthetic methods employed towards a range of highly complex protein-based research tools, and the advantages they bring to the research community.