Kinetics-based structural requirements of human immunoglobulin G binding peptides
Kinetics-based structural requirements of human immunoglobulin G binding peptides
复制标题
人免疫球蛋白 G 结合肽基于动力学的结构要求
DOI：
10.1021/acsomega.9b01104
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发表时间：
2019
期刊：
影响因子：
4.1
通讯作者：
Yoshio Hayashi
中科院分区：
文献类型：
--
作者：
Kyohei Muguruma;Konomi Fujita;Akane Fukuda;Satoshi Kishimoto;Soichiro Sakamoto;Risako Arima;Mayu Ito;Mayu Kawasaki;Shogo Nakano;Sohei Ito;Kanade Shimizu;Akihiro Taguchi;Kentaro Takayama;Atsuhiko Taniguchi;Yuji Ito;Yoshio Hayashi
目前，抗体不仅广泛应用于研究，也广泛应用于治疗。因此，选择性结合抗体片段结晶位点的肽已广泛应用于各种研究工作，例如制备抗体-药物偶联物（ADC）。因此，与免疫球蛋白G （IgG）结合的具有特定值和konandkoff值的适当肽将在不同的应用中有用，这些动力学参数可能被忽视，但它们是开发具有有利结合特性的肽配体的关键。我们制备了igg结合肽的结构衍生物1，并通过表面等离子体共振法和等温滴定量热法评估了产物的结合亲和力和动力学速率，以获得具有有益抗体结合特性的新型肽。这样，通过缩短的15-IgBP肽获得了15-Lys8Leuwith的快结合和缓释特性。另一方面，我们成功地获得了独特的肽，15-Lys8Tle，具有相似的kdvalue，但与15-IgBP相比，其konandkoff值相差高达6倍。这些新多肽可用于阐明对igg结合多肽功能的动力学效应，以及抗体或抗体-药物相互作用的各种应用，如免疫脂质体，ADC或半衰期延长策略，通过使用具有适当动力学特征的肽。
Currently, antibodies are widely used not only in research but also in therapy. Hence, peptides that selectively bind to the fragment crystallizable site of an antibody have been extensively utilized in various research efforts such as the preparation of antibody–drug conjugates (ADC). Consequently, appropriate peptides that bind to immunoglobulin G (IgG) with a specificKdvalue and alsokonandkoffvalues will be useful in different applications, and these kinetic parameters have been perhaps overlooked but are key to development of peptide ligands with advantageous binding properties. We prepared structural derivatives of IgG-binding peptide1and evaluated the binding affinity and kinetic rates of the products by surface plasmon resonance assay and isothermal titration calorimetry to obtain novel peptides with beneficial antibody binding properties. In this way,15-Lys8Leuwith fast-binding and slow-release features was obtained through a shortened peptide 15-IgBP. On the other hand, we successfully obtained distinctive peptide,15-Lys8Tle, with a similarKdvalue but withkonandkoffvalues that were as much as six-fold different from those of 15-IgBP. These new peptides are useful for the elucidation of kinetic effects on the function of IgG-binding peptides and various applications of antibody or antibody–drug interactions, such as immunoliposome, ADC, or half-life extension strategy, by using a peptide with the appropriate kinetic features.