Fc的MST-HN改造虽然能够有效地降低IgG水平,但是改造后的Efgartigimod在体内的半衰期显著下降。来自MedImmune的研究人员对Fc的改造进行了很多研究,他们发现,通过增强Fc与FcRn在酸性条件下的结合能够促进抗体在溶酶体的再循环利用,提高抗体半衰期,但这种提高不是无限度的,在...
The crystal structure of Fc-MST-HN in complex with FcRn provides a plausible explanation why the Fab disrupts the interaction only in the context of membrane-associated FcRn. Importantly, we find that Fc-MST-HN outperforms full-size IgG1-MST-HN in reducing IgG levels in cynomolgus monkeys. ...
以增强 FcRn 结合,从而延长 IgG 半衰期或强制 IgG 降解抗体;最好的例子是 IgG1 MST-HN变体,也称为 IgG1YTEKF (M252Y/S254T/T256E/H433K/N434F),它在酸性 pH 下与 FcRn 具有显着更高的结合,并在中性 pH 下保留结合,并且也称为增强 IgG 降解的抗体 (Abdeg)。
为了研究在pH 6.0和pH 7.4下任何组合变体是否显示出比MST-HN变体(在本文中称为“YTEKF基准”,其含有Met252、Ser254、Thr256、His433和Asn434到Tyr252、Thr254、Glu256、Lys433和Phe434的突变)更紧密的结合,进行以下方法。经由生物素CAPture方法进行生物素化人、食蟹猴和小鼠FcRn的捕获(参见图26的示意图)。对于...
作为阻止IgG和FcRn之间相互作用的替代方法,Patel et al.(J.Immunol.187:1015-1022,2011)报告了一种工程化的人IgG1抗体,具有增强的FcRn结合力;其在Fc区域中,在252位处Met取代了Tyr,在254位处Thr取代了Ser,在256位处Glu取代了Thr,在433位处Lys取代了His,且在434位处Phe取代了Asn(MST-HN;位置基于Eu编号),降...
Interestingly, a majority of the MST-HN residue changes provide additional hydrophobic contacts with (M253Y/S245T) or adjacent to (H433L/N434H) the FcRn hydrophobic patch centered around the C-terminal side of α-helix 1 and the N-terminal side of α-helix 2 (Fig. 4C). The Y256E ...
Solutions By company size Enterprises Small and medium teams Startups Nonprofits By use case DevSecOps DevOps CI/CD View all use cases By industry Healthcare Financial services Manufacturing Government View all industries View all solutions Resources Topics AI DevOps Security Softwar...
MST10RL-R01-03-100一体化振动温度变送器上润仪表 TM0393-A17-B00电机轴承振动传感器探头上润仪表 TKZZD-YB轴承防水振动变送器信号输出4-20mA上润仪表 JLGK-2480-508风机振动温度变送器二线制上润仪表 PCZ/S-V-00-01-00-00压缩机一体化振动变送器上润仪表 ZD-530汽轮机两线制一体化防水振动变...
qstieeqaktfldkfnheaedlfyqsslaswnyntniteenvqnmnnagdkwsaflkeqstlaqmyplqeiqnltvklqlqalqqngssvlsedkskrlntilntmstiystgkvcnpdnpqeclllepglneimansldynerlwaweswrsevgkqlrplyeeyvvlknemaranhyedygdywrgdyevngvdgydysrgqliedvehtfeeikplyehlhayvraklmnaypsyispigclpahllgdmwgrfwtnlysltvpfgqkpnidvtdamvdqawdaqrifkeaekf...
本发明的人ace2的胞外区氨基酸序列的非限制性实例如下[seq id no:1]:qstieeqaktfldkfnheaedlfyqsslaswnyntniteenvqnmnnagdkwsaflkeqstlaqmyplqeiqnltvklqlqalqqngssvlsedkskrlntilntmstiystgkvcnpdnpqeclllepglneimansldynerlwaweswrsevgkqlrplyeeyvvlknemaranhyedygdywrgdyevngvdgydysrgqliedvehtfeeikplyehlhayvr...