Identification of survival-promoting OSIP108 peptide variants and their internalization in human cells

Verbandt, Sara, Henriques, Sónia Troeira, Spincemaille, Pieter, Harvey, Peta J., Chandhok, Gursimran, Sauer, Vanessa, De Coninck, Barbara, Cassiman, David, Craik, David J., Cammue, Bruno P. A., De Cremer, Kaat and Thevissen, Karin (2017) Identification of survival-promoting OSIP108 peptide variants and their internalization in human cells. Mechanisms of Ageing and Development, 161 B: 247-254. doi:10.1016/j.mad.2016.07.013

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Author Verbandt, Sara
Henriques, Sónia Troeira
Spincemaille, Pieter
Harvey, Peta J.
Chandhok, Gursimran
Sauer, Vanessa
De Coninck, Barbara
Cassiman, David
Craik, David J.
Cammue, Bruno P. A.
De Cremer, Kaat
Thevissen, Karin
Title Identification of survival-promoting OSIP108 peptide variants and their internalization in human cells
Journal name Mechanisms of Ageing and Development   Check publisher's open access policy
ISSN 1872-6216
Publication date 2017-01-01
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.mad.2016.07.013
Open Access Status File (Author Post-print)
Volume 161
Issue B
Start page 247
End page 254
Total pages 8
Place of publication E Park, Shannon, Clare Ireland
Publisher Elsevier Ireland
Language eng
Abstract The plant-derived decapeptide OSIP108 increases tolerance of yeast and human cells to apoptosis-inducing agents, such as copper and cisplatin. We performed a whole amino acid scan of OSIP108 and conducted structure-activity relationship studies on the induction of cisplatin tolerance (CT) in yeast. The use of cisplatin as apoptosis-inducing trigger in this study should be considered as a tool to better understand the survival-promoting nature of OSIP108 and not for purposes related to anti-cancer treatment. We found that charged residues (Arg, His, Lys, Glu or Asp) or a Pro on positions 4–7 improved OSIP108 activity by 10% or more. The variant OSIP108[G7P] induced the most pronounced tolerance to toxic concentrations of copper and cisplatin in yeast and/or HepG2 cells. Both OSIP108 and OSIP108[G7P] were shown to internalize equally into HeLa cells, but at a higher rate than the inactive OSIP108[E10A], suggesting that the peptides can internalize into cells and that OSIP108 activity is dependent on subsequent intracellular interactions. In conclusion, our studies demonstrated that tolerance/survival-promoting properties of OSIP108 can be significantly improved by single amino acid substitutions, and that these properties are dependent on (an) intracellular target(s), yet to be determined.
Keyword Apoptosis-inducers
Cellular internalization
Structure activity relationship study
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID FL150100146
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
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