Development of a large peptoid-DOTA combinatorial library.
Development of a large peptoid-DOTA combinatorial library.
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DOI：
10.1002/bip.22883
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发表时间：
2016-09
期刊：
影响因子：
2.9
通讯作者：
Udugamasooriya, D. Gomika
中科院分区：
文献类型：
--
作者：
Singh, Jaspal;Lopes, Daniel;Udugamasooriya, D. Gomika
传统的单头单化合物（OBOC）文库合成通常用于鉴定具有治疗价值的分子。包含具有成像甚至潜在治疗和诊断能力的分子（例如治疗剂）的OBOC文库的设计和合成一直被忽视。针对特定目标开发具有内置成像组件的治疗活性分子是一项艰巨的任务，基于结构的合理设计可能不是最好的方法。我们假设开发一个组合文库，将潜在的治疗和成像成分融合在每个分子中。文库中的这些分子可用于筛选、识别和验证针对感兴趣目标的直接治疗候选物。作为实现这一目标的第一步，我们开发了一个包含153,600个肽类- DOTA化合物的头部文库，其中肽类是目标识别和潜在治疗成分，DOTA是成像成分。我们使用DOTA的四条臂中的一条将DOTA支架连接到TentaGel珠上，并在其余三条臂上构建了多样化的6 - mer肽库。我们评估了测试化合物和最终文库的合成和质谱测序能力。这些化合物显示出独特的电离模式，包括直接将DOTA支架断裂成两个单元，从而可以清楚地解码序列。我们的方法提供了一种简单的合成方法，用于完整地开发大型肽仿体- dota文库，用于筛选生物靶点，以确定未来潜在的治疗药物。©2016作者。Wiley期刊公司出版的生物聚合物。生物工程学报（自然科学版），2016,35(6):673-684。
Conventional one‐bead one‐compound (OBOC) library synthesis is typically used to identify molecules with therapeutic value. The design and synthesis of OBOC libraries that contain molecules with imaging or even potentially therapeutic and diagnostic capacities (e.g. theranostic agents) has been overlooked. The development of a therapeutically active molecule with a built‐in imaging component for a certain target is a daunting task, and structure‐based rational design might not be the best approach. We hypothesize to develop a combinatorial library with potentially therapeutic and imaging components fused together in each molecule. Such molecules in the library can be used to screen, identify, and validate as direct theranostic candidates against targets of interest. As the first step in achieving that aim, we developed an on‐bead library of 153,600 Peptoid–DOTA compounds in which the peptoids are the target‐recognizing and potentially therapeutic components and the DOTA is the imaging component. We attached the DOTA scaffold to TentaGel beads using one of the four arms of DOTA, and we built a diversified 6‐mer peptoid library on the remaining three arms. We evaluated both the synthesis and the mass spectrometric sequencing capacities of the test compounds and of the final library. The compounds displayed unique ionization patterns including direct breakages of the DOTA scaffold into two units, allowing clear decoding of the sequences. Our approach provides a facile synthesis method for the complete on‐bead development of large peptidomimetic–DOTA libraries for screening against biological targets for the identification of potential theranostic agents in the future. © 2016 The Authors. Biopolymers Published by Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 673–684, 2016.
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影响因子：
3.2
作者：
Fowler SA;Blackwell HE
通讯作者：
Blackwell HE
DOI：
10.1007/978-1-4939-2020-4_15
发表时间：
2015-01-01
期刊：
PEPTIDE LIBRARIES: METHODS AND PROTOCOLS
影响因子：
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作者：
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通讯作者：
Luyt, Leonard G.
影响因子：
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作者：
Green, M
通讯作者：
Green, M
影响因子：
4.3
作者：
Hummelen, JC;vanDongen, JLJ;Meijer, EW
通讯作者：
Meijer, EW
DOI：
10.1007/s10967-014-3672-2
发表时间：
2015-03-01
影响因子：
1.6
作者：
Audras, M.;Berthon, L.;Moisy, Ph
通讯作者：
Moisy, Ph