Immunoglobulin repertoires contain a fraction of antibodies that recognize low molecular weight compounds, including some enzymes cofactors, such as heme. Here, by using a set of 113 samples with variable region sequences matching clinical-stage antibodies, we demonstrated that a considerable number of these antibodies interact with heme. Antibodies that interact with heme possess specific sequence traits of their antigen-binding regions. Moreover they manifest particular physicochemical and functional qualities i.e. increased hydrophobicity, higher propensity of self-binding, higher intrinsic polyreactivity and reduced expression yields. Thus, interaction with heme is a strong predictor of different molecular and functional qualities of antibodies. Notably, these qualities are of high importance for therapeutic antibodies, as their presence was associated with failure of drug candidates to reach clinic. Our study reveled an important facet of information about relationship sequence-function in antibodies. It also offers a convenient tool for detection of liabilities of therapeutic antibodies.

中文翻译：

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临床阶段抗体与血红素的相互作用可预测其理化和结合质量

免疫球蛋白库包含一小部分识别低分子量化合物的抗体，其中包括一些酶辅因子，例如血红素。在这里，通过使用113个样本，这些样本具有与临床阶段抗体相匹配的可变区序列，我们证明了这些抗体中有相当数量与血红素相互作用。与血红素相互作用的抗体具有其抗原结合区的特定序列特征。此外，它们表现出特殊的物理化学和功能性质，即增加的疏水性，更高的自结合倾向，更高的固有多反应性和降低的表达产量。因此，与血红素的相互作用是抗体不同分子和功能质量的强烈预测因子。值得注意的是，这些质量对于治疗性抗体非常重要，因为他们的存在与候选药物未能到达诊所有关。我们的研究揭示了抗体中相关序列功能的重要信息。它还为检测治疗性抗体的负债提供了方便的工具。