Near-infrared triple-helical peptide with quenched fluorophores for optical imaging of MMP-2 and MMP-9 proteolytic activity in vivo

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:24

Article

Zhang, Xuan¹  Bresee, Jamee¹  Fields, Gregg B.²  Edwards, W. Barry¹ 

[1] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15219 USA

[2] Torrey Pines Inst Mol Studies, Port St Lucie, FL 34987 USA

关键词: Matrix metalloproteinase;    Gelatinase;    Triple-helical peptides;    Near-infrared (NIR) optical imaging;    Fluorescence molecular tomography (FMT);   

DOI  :  10.1016/j.bmcl.2014.06.072

来源: Elsevier

【 摘 要 】

The gelatinase members of the MMP family have consistently been associated with tumor invasiveness, which make them an attractive target for molecular imaging. We report new activatable proteolytic optical imaging agents that consist of triple-helical peptide (THP) conjugates, with high specificity to the gelatinases, bearing quenched cypate dyes. With quenching efficiencies up to 51%, the amplified fluorescence signal upon cypate(3)-THP hydrolysis by the gelatinases (k(cat)/K-M values of 6.4 x 10(3) M-1 s(-1) to 9.1 x 10(3) M-1 s(-1) for MMP-2 and MMP-9, respectively) in mice bearing human fibrosarcoma xenografted tumors was monitored with fluorescence molecular tomography. There was significant fluorescence enhancement within the tumor and this enhancement was reduced by treatment with pan-MMP inhibitor, Ilomastat. These data, combined with the gelatinase substrate specificity observed in vitro, indicated the observed fluorescence at the site of the tumor was due to gelatinase mediated hydrolysis of cypate(3)-THP. (C) 2014 Elsevier Ltd. All rights reserved.

【 授权许可】

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