Peptide Inhibitors of Xenoreactive Antibodies Mimic the Interaction Profile of the Native Carbohydrate Antigens
Peptide Inhibitors of Xenoreactive Antibodies Mimic the Interaction Profile of the Native Carbohydrate Antigens
复制标题
DOI：
10.1002/bip.21427
复制
发表时间：
2011-01-01
期刊：
影响因子：
2.9
通讯作者：
Yuriev, Elizabeth
中科院分区：
文献类型：
--
作者：
Agostino, Mark;Sandrin, Mauro S.;Yuriev, Elizabeth
碳水化合物-抗体相互作用介导许多细胞过程和免疫应答。在细胞表面上表达的碳水化合物充当特定细胞类型的识别元件，例如在ABO（H）血型系统中。识别宿主不相容的ABO（H）系统抗原的抗体存在于所有个体（AB个体除外）的血流中，防止不相容的供体和受体之间的输血和器官移植。跨物种移植（异种移植）也存在类似的障碍，特别是猪到人的移植。所有人都表达针对主要碳水化合物异种抗原Gal α（1，3）Gal（α Gal）的抗体，从而阻止成功的异种移植。尽管抗体结合位点被精确地组织以选择性地结合特定抗原，但许多抗体识别除其天然抗原以外的分子。已经鉴定了一系列可以模拟碳水化合物并抑制抗α Gal抗体的肽。然而，肽如何实现这一点的结构基础尚不清楚。以前，我们开发了一种计算机模拟方法，我们使用该方法来研究一组抗α Gal抗体对碳水化合物的识别。该方法涉及碳水化合物与抗体的分子对接，并使用对接的碳水化合物位姿来生成抗体结合位点在普遍氢键和货车范德华相互作用方面的图谱。我们已经应用这种方法来研究由抗cc Gal抗体识别的肽。发现肽和碳水化合物的位点图相似，表明肽与参与碳水化合物识别的相同残基相互作用。这项研究证明了抗碳水化合物抗体抑制剂的“绘图设计”的潜力。(C)2010 Wiley Periodicals，Inc. Biopolymers（Pept Sci）96：193-206，2011.
Carbohydrate-antibody interactions mediate many cellular processes and immune responses. Carbohydrates expressed on the surface of cells serve as recognition elements for particular cell types, for example, in the ABO(H) blood group system. Antibodies that recognize host-incompatible ABO(H) system antigens exist in the bloodstream of all individuals (except AB individuals), preventing blood transfusion and organ transplantation between incompatible donors and recipients. A similar barrier exists for cross-species transplantation (xenotransplantation), in particular for pig-to-human transplantation. All humans express antibodies against the major carbohydrate xenoantigen, Gal alpha(1,3)Gal (alpha Gal), preventing successful xenotransplantation. Although antibody binding sites are precisely organized so as to selectively bind a specific antigen, many antibodies recognize molecules other than their native antigen. A range of peptides have been identified that can mimic carbohydrates and inhibit anti-cc Gal antibodies. However, the structural basis of how the peptides achieved this was not known. Previously, we developed an in silico method which we used to investigate carbohydrate recognition by a panel of anti-cc Gal antibodies. The method involves molecular docking of carbohydrates to antibodies and uses the docked carbohydrate poses to generate maps of the antibody binding sites in terms of prevalent hydrogen bonding and van der Waals interactions. We have applied this method to investigate peptide recognition by the anti-cc Gal antibodies. It was found that the site maps of the peptides and the carbohydrates were similar, indicating that the peptides interact with the same residues as those involved in carbohydrate recognition. This study demonstrates the potential for "design by mapping" of anti-carbohydrate antibody inhibitors. (C) 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 193-206, 2011.