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Phototriggered release of tetrapeptide AAPV from coumarinyl and pyrenyl cages

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Abstract

Ala–Ala–Pro–Val (AAPV) is a bioactive tetrapeptide that inhibits human neutrophil elastase, an enzyme involved in skin chronic inflammatory diseases like psoriasis. Caged derivatives of this peptide were prepared by proper N- and C-terminal derivatisation through a carbamate or ester linkage, respectively, with two photoactive moieties, namely 7-methoxycoumarin-2-ylmethyl and pyren-2-ylmethyl groups. These groups were chosen to assess the influence of the photosensitive group and the type of linkage in the controlled photo release of the active molecule. The caged peptides were irradiated at selected wavelengths of irradiation (254, 300, and 350 nm), and the photolytic process was monitored by HPLC–UV. The results established the applicability of the tested photoactive groups for the release of AAPV, especially for the derivative bearing the carbamate-linked pyrenylmethyl group, which displayed the shortest irradiation times for the release at the various wavelengths of irradiation (ca. 4 min at 254 nm, 8 min at 300 nm and 46 min at 350 nm).

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Acknowledgements

Thanks are due to the Fundação para a Ciência e Tecnologia (FCT, Portugal) for financial support to the portuguese NMR network (PTNMR, Bruker Avance III 400-Univ. Minho), FCT and FEDER (European Fund for Regional Development)-COMPETE-QREN-EU for financial support through the Chemistry Research Centre of the University of Minho (Ref. UID/QUI/00686/2013 and UID/QUI/0686/2016). A PhD grant to A.M.S. (SFRH/BD/80813/2011) is also acknowledged.

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  1. Centre of Chemistry, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal

    Filipa C. Santos, Ana M. S. Soares, M. Sameiro T. Gonçalves & Susana P. G. Costa

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  1. Filipa C. Santos
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  2. Ana M. S. Soares
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  3. M. Sameiro T. Gonçalves
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  4. Susana P. G. Costa
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Correspondence to Susana P. G. Costa.

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Handling Editor: J. Bode.

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Santos, F.C., Soares, A.M.S., Gonçalves, M.S.T. et al. Phototriggered release of tetrapeptide AAPV from coumarinyl and pyrenyl cages. Amino Acids 49, 1077–1088 (2017). https://doi.org/10.1007/s00726-017-2405-6

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  • DOI: https://doi.org/10.1007/s00726-017-2405-6

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