Conotoxin engineering: dual pharmacophoric noradrenaline transport inhibitor/integrin binding peptide with improved stability

Organic & Biomolecular Chemistry
Zoltan DekanPaul F Alewood

Abstract

A dual-pharmacophoric peptide was engineered by grafting the integrin binding RGD motif between the C- and N-termini of a disulfide-rich noradrenaline transporter inhibiting χ-conotoxin resulting in a stable backbone cyclized peptide. The construct maintained two independent biological activities and showed increased plasma stability with no adverse effects observed following administration to rats, highlighting the potential value of pharmacophore grafting into constrained peptide scaffolds.

References

Jan 1, 1996·Annual Review of Cell and Developmental Biology·E Ruoslahti
May 10, 2001·The Journal of Biological Chemistry·R K AndrewsS P Watson
Apr 23, 2002·Current Medicinal Chemistry·Celine Adessi, Claudio Soto
Jan 2, 2003·Nature Reviews. Drug Discovery·Deepak L Bhatt, Eric J Topol
May 26, 2004·Biochemical Society Transactions·J Takagi
Jun 25, 2005·Current Medicinal Chemistry. Cardiovascular and Hematological Agents·X LuV V Kakkar
Aug 17, 2005·Journal of Thrombosis and Haemostasis : JTH·D R PhillipsP Andre
Aug 22, 2006·Current Pharmaceutical Design·X LuV V Kakkar
Oct 27, 2009·Journal of Molecular Biology·Christian P SommerhoffHarald Kolmar
Jan 12, 2012·Thrombosis and Haemostasis·Steen Dalby KristensenFranz-Josef Neumann

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Citations

Oct 19, 2012·Journal of the American Chemical Society·Sheng ZhangZhong-Yin Zhang
Nov 19, 2014·Future Medicinal Chemistry·Jutty Rajan PrashanthRichard J Lewis
Oct 16, 2012·Chemico-biological Interactions·Jon-Paul BinghamChino C Cabalteja
Aug 31, 2017·The Journal of Biological Chemistry·Xiaosa WuDavid J Craik

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