General lack of structural characterization of chemically synthesized long peptides.

Many peptide chemistry scientists have been reporting extremely interesting work on the basis of chemical peptides for which the only characterization was their purity, mass, and biological activity. It seems slightly overenthusiastic, as many of these structures should be thoroughly characterized first to demonstrate the uniqueness of the structure, as opposed to the uniqueness of the sequence. Among the peptides of identical sequences in the final chemical preparation, what amount of well-folded peptide supports the measured activity? The activity of a peptide preparation cannot prove the purity of the desired peptide. Therefore, greater care should be taken in characterizing peptides, particularly those coming from chemical synthesis. At a time when the pharmaceutical industry is changing its paradigm by moving substantially from small molecules to biologics to better serve patients' needs, it is important to understand the limitations of the descriptions of these products and to start to apply the same "good laboratory practices" to our peptide research. Here, we attempt to delineate how synthetic peptides are described and characterized and what will be needed to describe them in regards to how they are well-folded and homogeneous in their tertiary structure. Older studies were done when the tools were not yet discovered, but more recent publications are still lacking proper descriptions of these peptides. Modern tools of analysis are capable of segregating folded and unfolded peptides, even if the preparation is biologically active.