Synthesis and Characterization of Bradykinin Derivatives Based on a β-Cyclodextrin Core

Rachel J. Stephenson; Fran Wolber; Paul G. Plieger; David R. K. Harding

doi:10.1071/CH15460

RESEARCH ARTICLE

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Synthesis and Characterization of Bradykinin Derivatives Based on a β-Cyclodextrin Core

Rachel J. Stephenson ^A ^C ^D , Fran Wolber ^B , Paul G. Plieger ^A and David R. K. Harding ^A

+ Author Affiliations

- Author Affiliations

^A Institute of Fundamental Sciences, Massey University, Private Bag 11-222, Turitea Campus, Palmerston North 4442, New Zealand.

^B Institute of Food, Nutrition and Human Health, Massey University, Private Bag 11-222, Turitea Campus, Palmerston North 4442, New Zealand.

^C Current address: School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Qld 4072, Australia.

^D Corresponding author:. Email: r.stephenson@uq.edu.au

Australian Journal of Chemistry 69(3) 328-335 https://doi.org/10.1071/CH15460
Submitted: 28 July 2015 Accepted: 10 August 2015 Published: 4 September 2015

Abstract

Mono-6^A-fluorenylmethyloxycarbonylamino-mono-6^X-succinyl-β-cyclodextrin (1), an amino acid-based bi-functionalized derivative of β-cyclodextrin (β-CD), has been functionalized with the bioactive peptide, bradykinin and/or sulfonamides using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS). The all-in-one molecule contains a carrier (cyclodextrin), targeting agent (bradykinin), and/or model drug (sulfonamide). Varying combinations of these bradykinin-focussed molecules have been synthesized using Fmoc SPPS on Rink amide resin. The positioning of the sulfonamide group, the bradykinin peptide and the cyclodextrin carrier are essential for biological activity. The inclusion of spacers is also important. Structure–activity studies performed on three cancer cell lines in vitro support these conclusions.

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Synthesis and Characterization of Bradykinin Derivatives Based on a β-Cyclodextrin Core

Abstract

References

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