Peptidic Aldehydes Based on α- and β-Amino Acids: Synthesis, Inhibition of m-Calpain, and Anti-Cataract Properties

Richard J. Payne; Karina M. Brown; James M. Coxon; James D. Morton; Hannah Yun-Young Lee; Andrew D. Abell

doi:10.1071/CH04080

RESEARCH ARTICLE

Peptidic Aldehydes Based on α- and β-Amino Acids: Synthesis, Inhibition of m-Calpain, and Anti-Cataract Properties

Richard J. Payne ^A , Karina M. Brown ^A , James M. Coxon ^A , James D. Morton ^B , Hannah Yun-Young Lee ^B and Andrew D. Abell ^A ^C

+ Author Affiliations

- Author Affiliations

^A Department of Chemistry, University of Canterbury, Christchurch, New Zealand.

^B Animal and Food Sciences Division, Lincoln University, Canterbury, New Zealand.

^C Author to whom correspondence should be addressed (e-mail: andrew.abell@canterbury.ac.nz).

Australian Journal of Chemistry 57(9) 877-884 https://doi.org/10.1071/CH04080
Submitted: 23 March 2004 Accepted: 25 June 2004 Published: 1 September 2004

Abstract

We present a new synthesis of SJA6017 (a potent m-calpain inhibitor) and its adaptation in order to prepare analogues in which the constituent Leu and Val residues are systematically replaced with their corresponding β-amino acids and/or the N-terminal fluorophenylsulfonyl group is replaced by a water solubilizing N-pyridin-3-ylmethoxycarbonyl group. All compounds have been assayed against m-calpain, and the best inhibitor, SJA6017, has been shown to inhibit the development of opacity in a lens culture system design to mimic cataract.

Acknowledgments

We gratefully acknowledge a grant from the Foundation for Research Science and Technology. We also thank Drs Andrew McLeod and Peter Surman from Douglas Pharmaceuticals Ltd, Auckland, New Zealand, for helpful discussions.

^* It should be noted that 12a is less potent than 8a by a factor of four. Therefore, the effective concentration of 12a is less than 8a in these experiments.

References

Peptidic Aldehydes Based on α- and β-Amino Acids: Synthesis, Inhibition of m-Calpain, and Anti-Cataract Properties

Abstract

Acknowledgments

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