Some biomarkers are easier to find than others.  Once a class of molecules has been noticed, and the assay methodology to measure their levels has been optimized, data rapidly accumulates.  Related molecules frequently pop up (often as a result of artifacts appearing in the assays under certain conditions or when particular samples are analysed).  Its rather like unearthing an ancient pyramid – if the first dig identifies the tip of the pyramid, the rest follows quite quickly.
 

But imagine what it would be like trying to rebuild the pyramid if the blocks had been scattered over a wide area.  Finding one block wouldn’t necessarily help you find the next one.  That seems to be the case with the ever-growing superfamily of peptide modifications.  A trickle of discoveries of naturally occurring modifications of peptides is turning into a flood.  And the molecules that are being discovered seem to be associated with fascinating biology, and offer great promise as biomarkers now and in the future.
 

Modifications such as phosphorylation, sulphation, glycosylation and more recently glycation have been so extensively studied that they are taken for granted as part of the molecular landscape.  But the molecular diversity they generate is still under-appreciated.  Total Scientific have comprehensively analysed the unexpected array of natural antibodies against the oligosaccharides that decorate many extracellular proteins and peptides – and extended initial observations by others that changes in these anti-carbohydrate antibodies are useful biomarkers for the early stages of cancer development in man.  But even these studies, using multiplexed assays to profile the portfolio of anti-carbohydrate antibodies, hardly scratch the surface of the molecular diversity that exists in this domain.
 

Over the last decade the range of covalent tags on peptides and proteins has expanded much further.  The ubiquitin family of small peptide tags now numbers at least 46, and these can be added to proteins in a staggering variety of chains, ranging from a single ubiquitin tag to branched chains of different ubiquitin family members.  These modifications play central roles in diverse biological pathways, from cell division and organelle biogenesis to protein turnover and antigen presentation.  Our understanding of the importance of ubiquitinylation is progressing rapidly, but in the absence of good methodology to differentiate the vast diversity of tag structures the possibilities that proteins and peptides modified in this way may be valuable biomarkers is all but unexplored.
 

Covalent tags, such as phosphorylation, ubiquitination or nitrosylation, are not the only …

RxCelerate Ltd is an outsourced drug development platform based near Cambridge, UK. We specialize in delivering an entire road map of drug development services from discovery and medicinal chemistry through to formal preclinical development and clinical up to Phase IIa. In the last five years, we have witnessed dramatic changes in the drug development …