Effect of resins, solvents, and additives on aggregation

Numerous modified SPPS protocols have been suggested to improve the quality of difficult peptide syntheses. A common theme among the majority of these protocols is an attempt to limit the extent of p-sheet secondary structure formation by altering the solvation properties of the polymer, the polymer-bound protected peptide, and/or the surrounding reaction media. 

Each of the aforementioned modifications has undoubtedly provided improved crude products in a number of such syntheses. However, improved solvation of the polymer-peptide/reaction media, although extremely desirable, only aims to limit the effects and extent of p-sheet secondary structure formation. The potential for intermolecular backbone hydrogen bonding, the fundamental cause of the phenomenon, still exists. 

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