title: Design of a serum stability tag for bioactive peptides.
abstract: Serum has a high intrinsic proteolytic activity that leads to continuous processing of peptides and proteins. Strategies to protect bioactive peptides from serum proteolytic degradation include incorporation of unnatural amino acids, conformational constraints, large polymeric tags, or other synthetic manipulations such as amide bond replacements. Here we explored a possibility of designing a serum stability tag made of natural amino acids. We observed that a diproline motif (-Pro-Pro-) shows remarkable stability against serum endopeptidases. Accordingly, we designed close to 50 peptides to identify natural amino acids flanking the -Pro-Pro- sequence that can enhance the serum stability of this motif. As a result, a tetrapeptide with the sequence Asp-Pro-Pro-Glu (DPPE) was identified that remains intact in human serum for more than 24 h. at 37°C.
authors.forename: Kalyani
authors.initials: K
authors.lastname: Jambunathan
authors.affiliation: Center for Chemical Biology, SRI International, 140 Research Drive, Harrisonburg, VA 22802, USA. amit.galande@sri.com.
authors.forename: Amit K
authors.initials: AK
authors.lastname: Galande
mesh_terms: D000328:Adult; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D010450:Endopeptidases; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D010455:Peptides / Q000097:blood / Q000737:chemistry* / Q000378:metabolism*; D055550:Protein Stability; D059748:Proteolysis; D044967:Serum / Q000201:enzymology / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D010455:Peptides; D010450:Endopeptidases