生物谷報道:意大利米蘭圣菲爾德科研中心在《血液》雜志報道,,包含NGR模體的肽鏈能選擇性識別腫瘤新生血管,,可用于藥物靶向治療,。
Corti教授說,這些肽鏈與新生血管結合的特點是同內皮相關氨肽酶N(CD13)相互作用的結果,。近期研究顯示,,天冬酰胺脫酰胺作用可快速使NGR轉變成isoDGR(異天冬酰胺-甘氨酸-精氨酸),產生的αβ3配體影響內皮細胞功能和腫瘤生長,。
研究者關注NGR模體的結構和功能,,以及與其相關的血管生長性疾病的藥物研發(fā)。并進一步探索,,天然蛋白調控 NGR向isoDGR轉變時間依從性,,如纖維連接蛋白具有潛在“分子鐘”作用。(生物谷www.bioon.com)
生物谷推薦原始出處:
Blood , prepublished online June 23, 2008; DOI 10.1182/blood-2008-04-150862.Angelo Corti
The neovasculature homing motif NGR: more than meets the eye
Angelo Corti*, Flavio Curnis, Wadih Arap, and Renata Pasqualini
DIBIT-Department of Oncology, San Raffaele Scientific Institute, Milan, Italy
Genitourinary Medical Oncology and Cancer Biology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, United States
* Corresponding author; email: [email protected] .
A growing body of evidence suggests that peptides containing the NGR motif can selectively recognize tumor neovasculature and can be used, therefore, for ligand-directed targeted delivery of various drugs and particles to tumors or to other tissues with an angiogenesis component. The neovasculature binding properties of these peptides rely on the interaction with an endothelium-associated form of aminopeptidase N (CD13), an enzyme that has been implicated in angiogenesis and tumor growth. Recent studies have shown that NGR can rapidly convert to isoaspartate-glycine-arginine (isoDGR) by asparagine deamidation, generating v3 ligands capable of affecting endothelial cell functions and tumor growth. This review focuses on structural and functional properties of the NGR motif and its application in drug development for angiogenesis-dependent diseases. Furthermore, we discuss the time-dependent transition of NGR to isoDGR in natural proteins, such as fibronectins, and its potential role of as a "molecular timer" for generating new binding sites for integrins implicated in angiogenesis.