Disulfide rich peptides have gained significant attention recently due to their incredible biological stability and tolerance to epitope grafting. This class of peptides is often folded in solution, assuming the desired disulfide bond pattern correlates with the most thermodynamically stable structure. Sometimes though, especially for chemically synthesized cysteine rich peptides, this is not the case. The result is a complex mixture of peptides with varying disulfide bonding patterns and identical mass.
Using pairs of cysteine residues with matched orthogonal side chain protecting groups during chemical synthesis allows for precise regioselective control of the disulfide bond pattern on-resin, simplifying final purification steps. In today’s post, I’ll explore conditions for removing acetamidomethyl (Acm) protecting groups with simultaneous disulfide bond formation.
Continue reading Optimizing the removal of an Acm protecting group
As a chemist new to the peptide community, there are many choices that have to be made. Which coupling reagents to use? Heat or no heat to promote chemistry? And most importantly, which resin? I have talked previously about resin choices, from loading levels to swelling capacity and how they affect the synthesis outcome. But I haven’t addressed yet a fundamental feature of commercially available resins, and that’s the functional handle to which the peptide chain is conjugated.
In today’s post, I’ll describe some, and I mean only some, of the most commonly used chemical functionalities for Fmoc-based solid phase peptide synthesis and some scenarios in which you would choose one resin type over another.
Continue reading How to choose the right resin functionality for solid phase peptide synthesis