Université Paris Cité and Université de la Réunion and Université des Antilles, INSERM, BIGR, DSIMB, F-75014 Paris, France.
Université Paris Cité and Université de la Réunion and Université des Antilles, INSERM, BIGR, DSIMB, F-97715 Saint Denis Messag, France.
Int J Mol Sci. 2023 Sep 26;24(19):14586. doi: 10.3390/ijms241914586.
Camelids have the peculiarity of having classical antibodies composed of heavy and light chains as well as single-chain antibodies. They have lost their light chains and one heavy-chain domain. This evolutionary feature means that their terminal heavy-chain domain, VH, called VH here, has no partner and forms an independent domain. The VH is small and easy to express alone; it retains thermodynamic and interaction properties. Consequently, VHs have garnered significant interest from both biotechnological and pharmaceutical perspectives. However, due to their origin in , they cannot be used directly on humans. A humanization step is needed before a possible use. However, changes, even in the constant parts of the antibodies, can lead to a loss of quality. A dedicated tool, Llamanade, has recently been made available to the scientific community. In a previous paper, we already showed the different types of VH dynamics. Here, we have selected a representative VH and tested two humanization hypotheses to accurately assess the potential impact of these changes. This example shows that despite the non-negligible change (1/10th of residues) brought about by humanization, the effect is not drastic, and the humanized VH retains conformational properties quite similar to those of the camelid VH.
骆驼科动物具有独特的特性，其经典抗体由重链和轻链以及单链抗体组成。它们已经失去了轻链和一个重链结构域。这种进化特征意味着它们的末端重链结构域 VH（这里称为 VH）没有伴侣，形成一个独立的结构域。VH 很小，易于单独表达；它保留了热力学和相互作用特性。因此，VH 引起了生物技术和制药领域的极大兴趣。然而，由于它们起源于骆驼科动物，因此不能直接用于人类。在可能使用之前，需要进行人源化步骤。然而，即使在抗体的恒定部分发生变化，也可能导致质量损失。最近，一种名为 Llamanade 的专用工具已提供给科学界。在之前的一篇论文中，我们已经展示了不同类型的 VH 动力学。在这里，我们选择了一个代表性的 VH，并测试了两种人源化假设，以准确评估这些变化的潜在影响。这个例子表明，尽管人源化带来了不可忽视的变化（1/10 个残基），但影响并不剧烈，人源化的 VH 保留了与骆驼科 VH 相当相似的构象特性。
