Labeling peptides have been widely practiced in numerous applications in chemistry and biology.  For example, fluorescent dyes make peptides useful probes for in vitro and in vivo imaging and substrates for enzyme activity assays; biotinylation has vast applications including affinity-based purification of proteins, FRET-based flow cytometry and receptor localization; PEGylation enhances plasma half-life of peptides and proteins and stabilizes them against metabolic degradation; radiolabeled peptides are versatile probes for in vivo imaging and targeted radionuclide therapy and so on. Similarly, peptides bearing different labels serve as a powerful research tool since multiple labels bestow a variety of new functions. To the end, a number of orthogonal chemistries have been reported, such as click chemistry, thiol-maleimide chemistry, Staudinger ligation, and oxime/hydrazone formation. Despite the versatility and broad applications in traditional organic reactions, Suzuki-Miyaura coupling has been rarely used in peptide chemistry.  In addition, while these chemistries have been efficiently used alone in peptide conjugation and labeling, combination of orthogonal chemistries for multiple labeling of peptides is not so common.  We have developed an efficient synthetic method of carrying out Suzuki-Miyaura cross-coupling with peptides that gives in high yield and purity. Using it along with other orthogonal chemistries such as thiol-maleimide chemistry and click chemistry, we have developed chemistry and strategy to make multiple labeling of peptides. The feasibility of these orthogonal chemistries was demonstrated by labeling a peptide with a fluorescent dye, biotin, and PEG which can have many potential applications in biomedical research.

Multiple labeling of peptides via orthogonal chemistries

247th National Meeting (2014)

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