Biodistribution of the cyclotide MCoTI-II, a cyclic disulfide-rich peptide drug scaffold

Wang, Conan K., Stalmans, Sofie, De Spiegeleer, Bart and Craik, David J. (2016) Biodistribution of the cyclotide MCoTI-II, a cyclic disulfide-rich peptide drug scaffold. Journal of Peptide Science, 22 5: 305-310. doi:10.1002/psc.2862

Author Wang, Conan K.
Stalmans, Sofie
De Spiegeleer, Bart
Craik, David J.
Title Biodistribution of the cyclotide MCoTI-II, a cyclic disulfide-rich peptide drug scaffold
Journal name Journal of Peptide Science   Check publisher's open access policy
ISSN 1099-1387
Publication date 2016-05-01
Year available 2016
Sub-type Article (original research)
DOI 10.1002/psc.2862
Open Access Status Not Open Access
Volume 22
Issue 5
Start page 305
End page 310
Total pages 6
Place of publication Chichester, West Sussex United Kingdom
Publisher John Wiley & Sons
Language eng
Formatted abstract
Disulfide-rich macrocyclic peptides are promising templates for drug design because of their unique topology and remarkable stability. However, little is known about their pharmacokinetics. In this study, we characterize the biodistribution in mice of Momordica cochinchinensis trypsin inhibitor-II (MCoTI-II), a cyclic three-disulfide-containing peptide that has been used in a number of studies as a drug scaffold. The distribution of MCoTI-II was compared with that of chlorotoxin, which is a four-disulfide-containing peptide that has been used to develop brain tumor imaging agents; dermorphin, which is a disulfide-less peptide; and bovine serum albumin, a large protein. Both MCoTI-II and chlorotoxin distributed predominantly to the serum and kidneys, confirming that they are stable in serum and suggesting that they are eliminated from the blood through renal clearance. Although cell-penetrating peptides have been reported to be able to transport across the blood–brain barrier, MCoTI-II, which is a cell-penetrating peptide, showed no uptake into the brain. The uptake of chlorotoxin was higher than that of MCoTI-II but lower than that of dermorphin, which is considered to have low uptake into the brain. This study provides insight into the behavior of disulfide-rich peptides in vivo.
Keyword Bioavailability
Serum stability
Blood-brain barrier
Trypsin inhibitor
Cyclic peptide
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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