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Chemical re-engineering of chlorotoxin improves bioconjugation properties for tumor imaging and targeted therapy.

Abstract：

:Bioconjugates composed of chlorotoxin and near-infrared fluorescent (NIRF) moieties are being advanced toward human clinical trials as intraoperative imaging agents that will enable surgeons to visualize small foci of cancer. In previous studies, the NIRF molecules were conjugated to chlorotoxin, which results in a mixture of mono-, di-, and trilabeled peptide. Here we report a new chemical entity that bound only a single NIRF molecule. The lysines at positions 15 and 23 were substituted with either alanine or arginine, which resulted in only monolabeled peptide that was functionally equivalent to native chlorotoxin/Cy5.5. We also analyzed the serum stability and serum half-life of cyclized chlorotoxin, which showed an 11 h serum half-life and resulted in a monolabeled product. Based on these data, we propose to advance a monolabeled chlorotoxin to human clinical trials.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Akcan M,Stroud MR,Hansen SJ,Clark RJ,Daly NL,Craik DJ,Olson JM

doi

10.1021/jm101018r

subject

Has Abstract

pub_date

2011-02-10 00:00:00

pages

782-7

issue

3

eissn

0022-2623

issn

1520-4804

journal_volume

54

pub_type

杂志文章

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