Targeting beta-3 integrin using a linear hexapeptide labeled with a near-infrared fluorescent molecular probe

被引:27
作者
Bloch, Sharon [1 ]
Xu, Baogang [1 ]
Ye, Yunpeng [1 ]
Liang, Kexian [1 ]
Nikiforovich, Gregory V. [2 ]
Achilefu, Samuel [1 ]
机构
[1] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA
关键词
integrin; cancer; near-infrared; imaging; molecular probe;
D O I
10.1021/mp0600642
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Biomolecules containing the RGD peptide sequence are known to bind integrins with high affinity. Studies of hexa-and hepta-peptides labeled with a near-infrared fluorescent probe (cypate) showed that rearranging the glycine in a linear RGD peptide sequence to form the GRID analogue favored the uptake of the GIRD compound by a alpha(v)beta(3) integrin receptor (ABIR)-positive A549 tumor cells and tissue. The internalization of the GIRD compound in A549 cells and tumor uptake in mice were inhibited by ABIR-avid peptides, suggesting its recognition by this receptor. Further studies with functional blocking antibodies and beta(3) knockout cells revealed that beta(3) integrin mediates the internalization of the cypate-GRD peptide. Molecular modeling studies supported preferential interaction of the probe with the beta(3) subunit of integrins relative to the a subunit. The results demonstrate that the cypate-GRD peptide targets beta(3) integrin, thereby providing a strategy to monitor drug delivery and efficacy, and physiopathologic processes mediated by this protein.
引用
收藏
页码:539 / 557
页数:19
相关论文
共 91 条
[1]   Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging [J].
Achilefu, S ;
Dorshow, RB ;
Bugaj, JE ;
Rajagopalan, R .
INVESTIGATIVE RADIOLOGY, 2000, 35 (08) :479-485
[2]   Synergistic effects of light-emitting probes and peptides for targeting and monitoring integrin expression [J].
Achilefu, S ;
Bloch, S ;
Markiewicz, MA ;
Zhong, TX ;
Ye, YP ;
Dorshow, RB ;
Chance, B ;
Liang, KX .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (22) :7976-7981
[3]   Synthesis, in vitro receptor binding, and in vivo evaluation of fluorescein and carbocyanine peptide-based optical contrast agents [J].
Achilefu, S ;
Jimenez, HN ;
Dorshow, RB ;
Bugaj, JE ;
Webb, EG ;
Wilhelm, RR ;
Rajagopalan, R ;
Johler, J ;
Erion, JL .
JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (10) :2003-2015
[4]  
ALBELDA SM, 1990, CANCER RES, V50, P6757
[5]   In vitro and in vivo effects of a cyclic peptide with affinity for the αvβ3 integrin in human melanoma cells [J].
Allman, R ;
Cowburn, P ;
Mason, M .
EUROPEAN JOURNAL OF CANCER, 2000, 36 (03) :410-422
[6]   Integrin structure: new twists and turns in dynamic cell adhesion [J].
Arnaout, MA .
IMMUNOLOGICAL REVIEWS, 2002, 186 :125-140
[7]   Coming to grips with integrin binding to ligands [J].
Arnaout, MA ;
Goodman, SL ;
Xiong, JP .
CURRENT OPINION IN CELL BIOLOGY, 2002, 14 (05) :641-651
[8]  
Atherton E., 1989, SOLID PHASE PEPTIDE
[9]   ARG-GLY-ASP CONSTRAINED WITHIN CYCLIC PENTAPEPTIDES - STRONG AND SELECTIVE INHIBITORS OF CELL-ADHESION TO VITRONECTIN AND LAMININ FRAGMENT-P1 [J].
AUMAILLEY, M ;
GURRATH, M ;
MULLER, G ;
CALVETE, J ;
TIMPL, R ;
KESSLER, H .
FEBS LETTERS, 1991, 291 (01) :50-54
[10]   IS201, a specific αvβ3 integrin inhibitor, reduces glioma growth in vivo [J].
Bello, L ;
Lucini, V ;
Giussani, C ;
Carrabba, G ;
Pluderi, M ;
Scaglione, F ;
Tornei, G ;
Villani, R ;
Black, PM ;
Bikfalvi, A ;
Carroll, RS .
NEUROSURGERY, 2003, 52 (01) :177-185