Structural parameters modulating the cellular uptake of disulfide-rich cyclic cell-penetrating peptides: MCoTI-II and SFTI-1

D'Souza, Charlotte, Troeira Henriques, Sonia, Wang, Conan K. and Craik, David J. (2014) Structural parameters modulating the cellular uptake of disulfide-rich cyclic cell-penetrating peptides: MCoTI-II and SFTI-1. European Journal of Medicinal Chemistry, 88 10-18. doi:10.1016/j.ejmech.2014.06.047


Author D'Souza, Charlotte
Troeira Henriques, Sonia
Wang, Conan K.
Craik, David J.
Title Structural parameters modulating the cellular uptake of disulfide-rich cyclic cell-penetrating peptides: MCoTI-II and SFTI-1
Journal name European Journal of Medicinal Chemistry   Check publisher's open access policy
ISSN 0223-5234
1768-3254
Publication date 2014-06-23
Sub-type Article (original research)
DOI 10.1016/j.ejmech.2014.06.047
Volume 88
Start page 10
End page 18
Total pages 9
Place of publication Issy les Moulineaux, Cedex, France
Publisher Elsevier Masson
Collection year 2015
Language eng
Abstract Peptides are emerging as a new class of therapeutics due to their high potency and specificity for a range of targets, including the inhibition of protein-protein interactions. Disulfide-rich cyclic peptides, in particular, have attracted much attention in drug design due to their ultra-stable structure. Moreover, some of them have been shown to internalize into cells, which makes them potential scaffolds to deliver pharmaceutically bioactive sequences to intracellular targets. Here we examined the effects of structural modifications on the cell-penetrating properties of two disulfide-rich cyclic cell-penetrating peptides, Momordica cochinchinensis trypsin inhibitor II (MCoTI-II) and sunflower trypsin inhibitor-1 (SFTI-1). We found that the cellular uptake of MCoTI-II can be improved by increasing the overall positive charge of the native sequence. On the other hand, mutations to SFTI-1 did not significantly influence its cellular uptake, suggesting a non-specific endocytosis-dependent mechanism of cellular uptake. This study provides an understanding of the structural features affecting the internalization of MCoTI-II and SFTI-1, and hence provides a guide for the development of these disulfide-rich cyclic scaffolds into potential drug leads.
Keyword Cell-penetrating peptides
Flow cytometry
Nuclear magnetic resonance spectroscopy
Peptides
Solid-phase peptide synthesis
Surface plasmon resonance
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Sat, 30 Aug 2014, 00:49:16 EST by Susan Allen on behalf of Institute for Molecular Bioscience