In my lab we do a lot of peptide work with a particular emphasis on structure determination. This is a multistage and complex process that requires our utmost attention to detail, and is subject to many stumbling blocks of highly technical nature. The often capricious and solvent-dependent solubility and aggregation of peptides are enough to make me cringe. I can recall a number of occasions where we fell victims to this trap: we would change one amino acid in a sequence and record some utterly unanticipated behavior. For instance, one sequence would be soluble and well-behaved, whereas its close relative would be a complete “dud”. Welcome to the world of peptides! No wonder there is American Peptide Society out there… Have you heard of American Alkene Society? Or American Bromine Society? Nope, me neither. It tells you that peptide chemistry, as a field, is in a class of its own.

But let’s go back to some tangible ways of tackling peptide behavior, in particular peptide aggregation and solubility. I was reading a 5-year old paper by Geyer and colleagues in OBC, and came across the use of SDS in order to prevent self-aggregation of peptides. One of the sequences reported in this manuscript corresponded to a ten amino acid peptide with a high antiparallel amphipathic beta-sheet content. This peptide was inclined to self-aggregate in aqueous solution. Fortunately, this undesired behavior was effectively countered by adding perdeuterated sodium dodecyl sulfate to the aqueous phosphate buffer. Under these conditions, the precipitation was prevented, allowing the authors to study their molecules using NMR. I am going to discuss this property with my lab and see how SDS might help with some of our intractable cyclic peptide NMRs that occasionally raise their ugly heads. I think we need to compile a list of the magical additives that help avoid the pitfalls of peptide self-association. If you are aware of tricks along these lines, please let me know.

http://pubs.rsc.org/en/content/articlehtml/2010/ob/b917549k