Abstract
ß-Amino acids contain an extra carbon between the amino and carboxy-termini; this modification renders the adjacent peptide bond resistant to hydrolysis [1,2]. We hypothesize that substitution of the residues at the scissile bond with ß-amino acids can confer resistance to cleavage without necessarily abolishing binding to the enzyme. In the present study, we have synthesized a series of ß-amino acid-substituted analogues of bradykinin (BK), and examined both their susceptibility to cleavage by and their ability to inhibit the soluble metalloendopeptidases EC 3.4.24.15 (EP24.15) and EC 3.4.24.16 (EP24.16) [3]. Our findings suggest that ß-amino acid incorporation at the scissile bond completely prevents peptide hydrolysis with only minimal reduction in affinity for the enzyme.
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© 2001 Springer Science+Business Media Dordrecht
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Lew, R.A. et al. (2001). Use of β-Amino Acids in the Design of Substrate-Based Peptidase Inhibitors. In: Lebl, M., Houghten, R.A. (eds) Peptides: The Wave of the Future. American Peptide Symposia, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-0464-0_257
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DOI: https://doi.org/10.1007/978-94-010-0464-0_257
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-010-3905-5
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