Wikipedia

Photoactivated peptide

Photoactivated peptides are modified natural or synthetic peptides whose functions can be activated or controlled using light. These peptides incorporate light-sensitive elements that allow for precise regulation their biological activity in both space and time. The activation can be either irreversible, as in the case of caged peptides with photocleavable protecting groups,[1] or reversible, utilizing molecular photoswitches like azobenzenes or diarylethenes,[2][3][4] and diarylethenes[5][6] By incorporating these light-responsive components into the peptide structure, peptide properties, functions, and biological activities can be manipulated with high precision. This approach enables targeted activation of peptides in specific areas, making photoactivated peptides valuable tools for applications in cancer therapy, drug delivery, and probing molecular interactions in living cells and in organisms.[7][8][9]

Schematic representation of activation/deactivation of a photoswitchable peptide
A cartoon of a peptide with an azobenzene dye attached to the sidechains of cysteine residues. Exposure to 360 nm light causes photoisomerization of the diazo dye from E to Z, shortening it and encouraging a more alpha-helical conformation

Applications

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Photoactivated peptides have shown potential for various applications, including cancer therapy, other light-controlled drugs, and as tools to probe molecular interactions in intact cells and whole organisms.[8]

Initial studies demonstrated that these peptides could effectively kill B-cell lymphoma cancer cells. Specifically, a synthetic short peptide was alkylated with azobenzene crosslinkers and used to photo-stimulate mitochondrial membrane depolarization and cytochrome c release in permeabilized cells, initiating the intrinsic apoptosis pathway.[8] Analogs of Gramicidin S containing a diarylethene fragment[6] have also been developed, exhibiting a clear, reversible change in antimicrobial activity. In their inactive, UV-inducible photoform, these analogs are harmless to bacteria cells; however, upon activation with visible (amber) light, they become bactericidal. Additionally, a photoswitchable analogue of the orexin-B peptide has been developed, enabling control of orexin receptors with light in vivo at nanomolar concentrations.[10]

Photoswitchable peptides have been designed to inhibit protein-protein interactions in a light-controlled manner. They have been successfully applied to inhibit clathrin-mediated endocytosis in mammalian cells[11][12] and in yeast.[13] This same design principle has been applied to inhibit protein-protein interactions involved in cancer[14] and can potentially be used for any interaction mediated by a helical motif.

See also

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References

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  1. ^ Umezawa N, Noro Y, Ukai K, Kato N, Higuchi T (July 2011). "Photocontrol of Peptide function: backbone cyclization strategy with photocleavable amino Acid". ChemBioChem. 12 (11): 1694–1698. doi:10.1002/cbic.201100212. PMID 21656633. S2CID 38514167.
  2. ^ Abell AD, Jones MA, Neffe AT, Aitken SG, Cain TP, Payne RJ, et al. (June 2007). "Investigation into the P3 binding domain of m-calpain using photoswitchable diazo- and triazene-dipeptide aldehydes: new anticataract agents". Journal of Medicinal Chemistry. 50 (12): 2916–2920. doi:10.1021/jm061455n. PMID 17497840.
  3. ^ Kuil J, van Wandelen LT, de Mol NJ, Liskamp RM (October 2009). "Switching between low and high affinity for the Syk tandem SH2 domain by irradiation of azobenzene containing ITAM peptidomimetics". Journal of Peptide Science. 15 (10): 685–691. doi:10.1002/psc.1173. PMID 19714714. S2CID 26093872.
  4. ^ Woolley GA, Jaikaran AS, Berezovski M, Calarco JP, Krylov SN, Smart OS, et al. (May 2006). "Reversible photocontrol of DNA binding by a designed GCN4-bZIP protein". Biochemistry. 45 (19): 6075–6084. CiteSeerX 10.1.1.555.8745. doi:10.1021/bi060142r. PMID 16681380.
  5. ^ Fujimoto K, Kajino M, Sakaguchi I, Inouye M (August 2012). "Photoswitchable, DNA-binding helical peptides assembled with two independently designed sequences for photoregulation and DNA recognition". Chemistry. 18 (32): 9834–9840. doi:10.1002/chem.201201431. PMID 22767420.
  6. ^ a b Babii O, Afonin S, Berditsch M, Reisser S, Mykhailiuk PK, Kubyshkin VS, et al. (March 2014). "Controlling biological activity with light: diarylethene-containing cyclic peptidomimetics". Angewandte Chemie. 53 (13): 3392–3395. doi:10.1002/anie.201310019. PMID 24554486.
  7. ^ Zhang Y, Erdmann F, Fischer G (October 2009). "Augmented photoswitching modulates immune signaling". Nature Chemical Biology. 5 (10): 724–726. doi:10.1038/nchembio.214. PMID 19734911.
  8. ^ a b c Mart RJ, Errington RJ, Watkins CL, Chappell SC, Wiltshire M, Jones AT, et al. (November 2013). "BH3 helix-derived biophotonic nanoswitches regulate cytochrome c release in permeabilised cells". Molecular BioSystems. 9 (11): 2597–2603. doi:10.1039/C3MB70246D. PMID 23942570.
  9. ^ Mart RJ, Errington RJ, Watkins CL, Chappell SC, Wiltshire M, Jones AT, et al. (November 2013). "BH3 helix-derived biophotonic nanoswitches regulate cytochrome c release in permeabilised cells". Molecular BioSystems. 9 (11): 2597–2603. doi:10.1039/C3MB70246D. PMID 23942570.
  10. ^ Prischich D, Sortino R, Gomila-Juaneda A, Matera C, Guardiola S, Nepomuceno D, et al. (July 2024). "In vivo photocontrol of orexin receptors with a nanomolar light-regulated analogue of orexin-B". Cellular and Molecular Life Sciences. 81 (1): 288. doi:10.1007/s00018-024-05308-x. PMC 11335211. PMID 38970689.
  11. ^ Nevola L, Martín-Quirós A, Eckelt K, Camarero N, Tosi S, Llobet A, et al. (July 2013). "Light-regulated stapled peptides to inhibit protein-protein interactions involved in clathrin-mediated endocytosis". Angewandte Chemie. 52 (30): 7704–7708. doi:10.1002/anie.201303324. PMID 23775788.
  12. ^ Martín-Quirós A, Nevola L, Eckelt K, Madurga S, Gorostiza P, Giralt E (January 2015). "Absence of a stable secondary structure is not a limitation for photoswitchable inhibitors of β-arrestin/β-Adaptin 2 protein-protein interaction". Chemistry & Biology. 22 (1): 31–37. doi:10.1016/j.chembiol.2014.10.022. PMID 25615951.
  13. ^ Prischich D, Camarero N, Encinar Del Dedo J, Cambra-Pellejà M, Prat J, Nevola L, et al. (October 2023). "Light-dependent inhibition of clathrin-mediated endocytosis in yeast unveils conserved functions of the AP2 complex". iScience. 26 (10): 107899. doi:10.1016/j.isci.2023.107899. PMC 10520943. PMID 37766990.
  14. ^ Nevola L, Varese M, Martín-Quirós A, Mari G, Eckelt K, Gorostiza P, et al. (January 2019). "Targeted Nanoswitchable Inhibitors of Protein-Protein Interactions Involved in Apoptosis". ChemMedChem. 14 (1): 100–106. doi:10.1002/cmdc.201800647. PMID 30380184. S2CID 53177026.
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