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

Zoltan Dekan; Ching I Anderson Wang; Robert K. Andrews; Richard J Lewis; Paul F Alewood

doi:10.1039/c2ob25133g

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

Zoltan Dekan, Ching I Anderson Wang, Robert K. Andrews, Richard J Lewis, Paul F Alewood

Australian Centre for Blood Diseases

Research output: Contribution to journal › Article › Other › peer-review

11 Citations (Scopus)

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.

Original language	English
Pages (from-to)	5791-5794
Number of pages	4
Journal	Organic & Biomolecular Chemistry
Volume	10
Issue number	30
DOIs	https://doi.org/10.1039/c2ob25133g
Publication status	Published - 14 Aug 2012

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10.1039/c2ob25133g

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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.",

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AU - Lewis, Richard J

AU - Alewood, Paul F

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

Abstract

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