Discovery of a phosphatidylserine-recognizing peptide and its utility in molecular imaging of tumour apoptosis.
Discovery of a phosphatidylserine-recognizing peptide and its utility in molecular imaging of tumour apoptosis.
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DOI：
10.1111/j.1582-4934.2008.00305.x
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发表时间：
2008-09
影响因子：
5.3
通讯作者：
Kim IS
中科院分区：
文献类型：
--
作者：
Thapa N;Kim S;So IS;Lee BH;Kwon IC;Choi K;Kim IS
磷脂酰丝氨酸（PS）分子从质膜内层到外层的暴露已被认为是细胞凋亡过程中明确的分子表位。 PS 暴露的检查和监测是各种临床条件下非侵入性细胞凋亡成像中广泛使用的分子标记，包括评估治疗性抗癌药物和心肌梗塞。在此，我们报告了 PS 识别肽的鉴定，该肽是通过在 PS 包被的 ELISA 板上筛选 M13 噬菌体展示肽库来鉴定的。总共四轮的重复生物淘选揭示了展示肽序列 CLSYYPSYC (46%) 的噬菌体克隆的主要富集。鉴定出的噬菌体克隆证明与非凋亡细胞相比与许多凋亡细胞的结合增强，并且这种结合被噬菌体上展示的膜联蛋白 V 和合成肽抑制。通过 FACS 分析和荧光显微镜评估荧光素标记的 CLSYYPSYC 肽与凋亡细胞和正常细胞的结合。对用单剂量抗癌药物（camp-tothecin）治疗的荷瘤裸鼠（H460细胞异种移植模型）全身施用荧光素标记的 CLSYYPSYC 肽后的光学成像表明肽归巢至肿瘤。肿瘤组织的组织学检查显示肿瘤脉管系统和凋亡肿瘤细胞的强烈染色。根据这些结果，CLSYYPSYC 肽被认为是一种新型 PS 识别部分，有可能开发成用于体内凋亡成像的分子探针。该应用显然与肿瘤抗癌治疗功效的评估相关。
The exposure of phosphatidylserine (PS) molecules from the inner to the outer leaflet of the plasma membrane has been recognized as a well-defined molecular epitope of cells undergoing apoptosis. Examination and monitoring of PS exposure is an extensively used molecular marker in non-invasive apoptosis imaging under a variety of clinical conditions, including the assessment of therapeutic anti-cancer agents and myocardial infarction. Herein, we report the identification of a PS-recognizing peptide which was identified by the screening of an M13 phage display peptide library onto PS-coated ELISA plates. Repeated biopanning for a total of four rounds revealed a predominant enrichment of the phage clone displaying peptide sequence, CLSYYPSYC (46%). The identified phage clone evidenced enhanced binding to a number of apoptotic cells over non-apoptotic cells, and this binding was inhibited by both annexin V and synthesized peptide displayed on the phage. The binding of the fluorescein-labelled CLSYYPSYC peptide to apoptotic versus normal cells was assessed by both FACS analysis and fluorescence microscopy. Optical imaging after the systemic administration of fluorescein-labelled CLSYYPSYC peptide to tumour-bearing nude mice (H460 cells xenograft model) treated with a single dose of an anticancer drug (camp-tothecin) indicated peptide homing to the tumour. The histological examination of tumour tissues showed intense staining of the tumour vasculature and apoptotic tumour cells. With these results, the CLSYYPSYC peptide is recognized as a novel PS-recognizing moiety which may possibly be developed into a molecular probe for the imaging of apoptosis in vivo. This application would clearly be relevant to assessments of the efficacy of anticancer therapy in tumours.
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影响因子：
3.2
作者：
DiVittorio, KM;Johnson, JR;Smith, BD
通讯作者：
Smith, BD
影响因子：
7.8
作者：
Dasgupta, Swapan K.;Guchhait, Prasenjit;Thiagarajan, Perlimal
通讯作者：
Thiagarajan, Perlimal
影响因子：
--
作者：
Laumonier, Catherine;Segers, Jerome;Muller, Robert N.
通讯作者：
Muller, Robert N.
影响因子：
2.9
作者：
Kimura, Tomohiro
通讯作者：
Kimura, Tomohiro
影响因子：
9.9
作者：
Lampl, Y;Lorberboym, M;Gilad, R
通讯作者：
Gilad, R