Distribution of immunoglobulin Fab fragment conjugated with HIV-1 REV peptide following intravenous administration in rats
Distribution of immunoglobulin Fab fragment conjugated with HIV-1 REV peptide following intravenous administration in rats
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DOI：
10.1021/mp050064m
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发表时间：
2006-03-01
影响因子：
4.9
通讯作者：
Futaki, Shiroh
中科院分区：
文献类型：
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作者：
Kameyama, Shouju;Okada, Ritsuko;Futaki, Shiroh
HIV-1 Rev多肽(34-50位)是众所周知的细胞渗透性多肽。在本研究中，我们研究了免疫球蛋白与Rev肽结合的Fab片段(Rev-Fab)在大鼠静脉注射后的分布，并与天然Fab片段(NFab)进行了比较。放射性碘标记的Rev-Fab或nFab(分别为I-125-Rev-Fab或I-125-nFab)单次静脉注射2 mg/kg(3MBq/kg)。给药后测定血中总放射性和三氯乙酸不溶性放射性浓度、全身放射自显影(ARG)和尿排泄率。在血液和血浆方面，I-125-Rev-Fab的总放射性浓度和TCA不溶性放射性浓度显著低于I-125-nFab。在给药后4h的全身ARG中，I-125-Rev-Fab在肾上腺、脾和肝脏的放射性显著高于I-125-nFab。关于尿排泄率，这两个样本在给药后24小时，大约70%的放射性剂量以低分子成分的形式排出。大鼠静脉注射I-125-Rev-Fab后，可迅速从血液渗透到肾上腺、脾、肝脏等组织，并不停留在原地，24小时后主要经肾途径被消化和排泄，这些特点使细胞渗透肽有望为新型抗体药物的开发提供帮助。
HIV-1 REV peptide (positions 34-50) is well-known as a cell-permeating peptide. In this study, we investigated the distribution of Fab fragment of immunoglobulin conjugated with REV peptide (REV-Fab) following intravenous administration in rats, and compared with those of the native Fab fragment (nFab). Radioiodinated REV-Fab or nFab (I-125-REV-Fab or I-125-nFab, respectively) was given in a single intravenous dose of 2 mg/kg (3 MBq/kg). Total radioactive and TCA-insoluble radioactive concentrations in blood, whole-body autoradiography (ARG), and urinary excretion rates were assayed following administration. Regarding blood and plasma, total radioactive and TCA-insoluble radioactive concentrations for I-125-REV-Fab were remarkably lower than those for I-125-nFab. In the whole-body ARG at 4 h after administration, I-125-REV-Fab produced remarkably higher radioactivity in the adrenal gland, spleen, and liver, compared to I-125-nFab. Regarding urinary excretion rates, approximately 70% of the radioactive dose was excreted in the form of a low-molecular-weight component by 24 h after administration for both samples. I-125-REV-Fab may penetrate quickly from blood to adrenal gland, spleen, liver, and other tissues after intravenous administration to rats, and then did not stay in situ and was digested and excreted mostly via the renal route by 24 h. With these features, cell-permeating peptides are expected to help the development of new antibody pharmaceuticals.