N-Linked Glycosylated β-Peptides Are Resistant to Degradation by Glycoamidase A

✍ Scribed by Matthew D. Disney; David F. Hook; Kenji Namoto; Peter H. Seeberger; Dieter Seebach

• Book ID: 101769485
• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: English
• Weight: 197 KB
• Volume: 2
• Category: Article
• ISSN: 1612-1872
• DOI: 10.1002/cbdv.200590132

✦ Synopsis

b-Peptides are resistant to degradation by a variety of proteolytic enzymes that rapidly degrade natural apeptides. This is one of many characteristics that make b-peptides an attractive class of compounds for drug discovery efforts. To further understand the molecular recognition properties of b-peptides and the ability of enzymes to degrade them, we have synthesized a series of N-linked glycosylated band a-peptides, and tested their stability towards a glycosidase. We found that glyco-b-peptides that contain N-acetylglucosamine (1) or N,N-diacetylchitobiose (2) are completely stable to degradation by glycoamidase A. In comparison, the glyco-apeptides 3 and 4 containing N-acetylglucosamine or N,N-diacetylchitobiose are degraded. Inhibition experiments using increasing concentrations of a glyco-b-peptide fail to inhibit degradation of the corresponding glyco-a-peptide, even when the glyco-b-peptide is at a 128-fold higher concentration than the glyco-a-peptide. Evidently, the glyco-b-peptides have a much weaker affinity for the active site of the glycosidase than the corresponding glyco-a-peptide. These and the results with proteolytic enzymes suggest that the additional CH 2 group introduced into the a-amino acid residues causes b-peptides not to be recognized by hydrolytic enzymes. The results described herein suggest the potential of b-peptides that are functionalized with carbohydrates for biological and biomedical investigations, without having to be concerned about the carbohydrate being removed.