Chemical re-engineering of chlorotoxin improves bioconjugation properties for tumor imaging and targeted therapy.
Chemical re-engineering of chlorotoxin improves bioconjugation properties for tumor imaging and targeted therapy.
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DOI：
10.1021/jm101018r
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发表时间：
2011-02-10
影响因子：
7.3
通讯作者：
Olson JM
中科院分区：
文献类型：
--
作者：
Akcan M;Stroud MR;Hansen SJ;Clark RJ;Daly NL;Craik DJ;Olson JM
由氯毒素和近红外荧光（NIRF）组成的生物偶联物正在向人类临床试验迈进，作为术中显像剂，使外科医生能够看到癌症的小病灶。在以前的研究中，NIRF分子与氯毒素结合，从而产生单、二、三标记肽的混合物。在这里，我们报道了一个新的化学实体，它只结合一个单一的NIRF分子。在位置15和23的赖氨酸被Ala或Arg取代，得到一个功能相当于天然氯毒素的单标记肽：Cy5.5。我们还分析了环化氯毒素的血清稳定性和血清半衰期，结果表明环化氯毒素的血清半衰期为11小时。基于这些数据，我们建议将单标记氯毒素推向人体临床试验。
Bioconjugates composed of chlorotoxin and near infrared fluorescent (NIRF) moieties are being advanced toward human clinical trials as intra-operative imaging agents that will enable surgeons to visualize small foci of cancer. In previous studies, the NIRF molecules were conjugated to chlorotoxin, which results in a mixture of mono-, di-, and tri-labeled peptide. Here we report a new chemical entity that bound only a single NIRF molecule. The lysines at positions 15 and 23 were substituted with either Ala or Arg, which resulted in only mono-labeled peptide that was functionally equivalent to native chlorotoxin:Cy5.5. We also analyzed the serum stability and serum half life of cyclized chlorotoxin, which showed an 11 hour serum half life and resulted in a mono-labeled product. Based on these data, we propose to advance a mono-labeled chlorotoxin to human clinical trials.
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