Combinatorial peptide libraries: mining for cell-binding peptides.
Combinatorial peptide libraries: mining for cell-binding peptides.
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DOI：
10.1021/cr400166n
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发表时间：
2014-01-22
期刊：
影响因子：
62.1
通讯作者：
Brown, Kathlynn C.
中科院分区：
文献类型：
--
作者：
Gray, Bethany Powell;Brown, Kathlynn C.
细胞的表面代表了大分子的集合，它为细胞提供了一种独特的细胞景观，这是细胞的类型和状态所特有的。区分细胞表面表型细微差异的配体在各种各样的研究和临床应用中都有实用价值。特别是，能够将生物活性货物运送到特定细胞类型或患病细胞的细胞结合配体受到高度关注。虽然灵丹妙药的概念是由保罗·埃利希在一个多世纪前提出的，但科学界尚未完全实现这一目标。(1)这主要是因为在获得具有必要辨别能力的高亲和力细胞结合配体方面存在障碍。考虑到人体包含210种不同的细胞（不包括病变细胞），由10 ~ 14个细胞组成，问题的难度可想而知。此外，一旦分离，配体必须能够大量制备，必须能够进行化学修饰以获得最佳的体内生物分布，并且必须能够定制以适应各种临床应用。由于抗体通常对其靶标具有高亲和力和特异性，它们作为细胞靶向药物引起了人们的关注。单克隆抗体（mab）可以针对差异表达的细胞表面特征产生，并且fda批准的与细胞表面抗原结合的单克隆抗体的数量持续增长。(2)单抗疗法用于治疗多种疾病。然而，大多数临床批准的治疗性单克隆抗体不与药物或毒素结合，因此属于分子靶向治疗的范畴。这种抗体通过阻断受体的活性或激活免疫系统来破坏抗体靶标而被动发挥作用。(3)只有少数临床批准的单克隆抗体携带可交付物。例如，两种放射性标记抗体Zevalin （ibritumomab tiuxetan）和Bexxar（碘-131 tositumomab）已在美国获得批准；两者都是抗cd20抗体，用于非霍奇金淋巴瘤患者。美国唯一临床批准的抗体-药物结合物是Adcetris （brentuximab vedotin）。Adcetris于2011年获批，是一种抗cd30抗体，与高毒性微管破坏剂单甲基auristatin E偶联，用于治疗霍奇金淋巴瘤（HL）或系统性间变性大细胞淋巴瘤（sALCL）。最近，一种calicheamicin抗cd33抗体缀合物Mylotarg在临床试验10年后因未显示出疗效而被撤出市场。
The surface of a cell represents a collection of macromolecules, which provides the cell with a unique cellular landscape specific to the type and state of the cell. Ligands that discriminate between subtle differences in cell surface phenotypes have utility in a wide variety of research and clinical applications. In particular, cell-binding ligands that can deliver biologically active cargo to a specific cell type or a diseased cell are highly sought. While the concept of the magic bullet drug was introduced by Paul Erlich over a century ago, the scientific community has yet to fully realize this goal.(1) This stems primarily from hurdles in obtaining high-affinity cell-binding ligands with the necessary discriminating power. The difficulty of the problem is realized by considering that the human body contains 210 distinct cell types, not including diseased cells, and is composed of∼ 10 14 cells. Furthermore, once isolated, the ligand must be able to be prepared in large quantities, must be amenable to chemical modification for optimal in vivo biodistribution, and must be able to be tailored to suit a variety of clinical applications.As antibodies typically have high affinity and specificity for their targets, they have garnered attention as cell-targeting agents. Monoclonal antibodies (mAbs) can be generated against differentially expressed cell surface features, and the number of FDA-approved mAbs that bind to cell surface antigens continues to grow.(2) mAb therapies are used to treat a variety of diseases. However, most of the clinically approved therapeutic mAbs are not conjugated to drugs or toxins and therefore fall into the category of molecularly targeted therapies. Such antibodies function passively by either blocking the activity of receptors or activating the immune system to destroy the antibody target.(3) Only a few clinically approved mAbs carry a deliverable. For example, two radiolabeled antibodies, Zevalin (ibritumomab tiuxetan) and Bexxar (iodine-131 tositumomab), are approved in the United States; both are anti-CD20 antibodies used for select patients with non-Hodgkin’s lymphoma. The only clinically approved antibody–drug conjugate in the United States is Adcetris (brentuximab vedotin). Approved in 2011, Adcetris is an anti-CD30 antibody conjugated to the highly toxic microtubule-disrupting agent monomethyl auristatin E and is utilized for the treatment of Hodgkin’s lymphoma (HL) or systemic anaplastic large-cell lymphoma (sALCL). Mylotarg, a calicheamicin anti-CD33 antibody conjugate, was recently removed from the market after 10 years in the clinic for failing to show efficacy.
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影响因子：
17.1
作者：
Ashley CE;Carnes EC;Phillips GK;Durfee PN;Buley MD;Lino CA;Padilla DP;Phillips B;Carter MB;Willman CL;Brinker CJ;Caldeira Jdo C;Chackerian B;Wharton W;Peabody DS
通讯作者：
Peabody DS
影响因子：
20.3
作者：
Agemy, Lilach;Sugahara, Kazuki N.;Ruoslahti, Erkki
通讯作者：
Ruoslahti, Erkki
DOI：
10.1073/pnas.152463399
发表时间：
2002-10-01
影响因子：
11.1
作者：
Åkerman, ME;Chan, WCW;Ruoslahti, E
通讯作者：
Ruoslahti, E
影响因子：
4.7
作者：
Aggarwal, S;Harden, JL;Denmeade, SR
通讯作者：
Denmeade, SR
DOI：
10.1073/pnas.241655998
发表时间：
2002-02-05
影响因子：
11.1
作者：
Arap, W;Haedicke, W;Ruoslahti, E
通讯作者：
Ruoslahti, E