化学位移是核磁共振波谱(nuclear magnetic resonance spectrum,NMR)的一项重要参数,由于其对原子周围化学环境十分敏感,因此化学位移的理论计算在生物大分子的结构预测中扮演着重要的角色[1-2]。目前预测生物大分子NMR化学位移的理论...化学位移是核磁共振波谱(nuclear magnetic resonance spectrum,NMR)的一项重要参数,由于其对原子周围化学环境十分敏感,因此化学位移的理论计算在生物大分子的结构预测中扮演着重要的角色[1-2]。目前预测生物大分子NMR化学位移的理论方法主要分为两类:一类是从实验数据拟合得到的经验或者半经验方法[3-4];另一类是基于量子力学理论的从头计算方法[5-7]。与前者相比,量子力学方法不依赖数据集,针对不同体系具有很好的移植性。由于量子力学方法需要的计算时间随计算体系的大小呈多项式增长,因此人们基于“化学局域性”原理发展了分块量子化学方法来提高计算效率。本课题组长期致力于分块量子化学方法的发展,针对生物大分子的NMR化学位移精确预测发展了自动分块的大分子NMR化学位移计算方法(automated fragmentation,AF-NMR)。本文简要介绍本课题组在这方面的研究进展。展开更多
Camrelizumab is a humanized monoclonal antibody(m Ab)against human PD-1.It demonstrated a single digit nanomolar binding affinity to human and cynomolgus monkey PD-1,but no cross-reactivity to murine PD-1.It exhibited...Camrelizumab is a humanized monoclonal antibody(m Ab)against human PD-1.It demonstrated a single digit nanomolar binding affinity to human and cynomolgus monkey PD-1,but no cross-reactivity to murine PD-1.It exhibited potent PD-1/PD-L1 blocking activity as well as the T cell activation in vitro.The distinct binding sites of cameralizumab were perfectly overlapped with the PD-L1 binding sites,which supported its excellent ability in blocking PD-1/PD-L1 interaction.It also significantly inhibited the growth of murine MC-38 and B16 F10 cell in humanized PD-1 transgenic mice with a superior inhibitory effect compared with the other marketed anti-PD-1 antibodies.Furthermore,camrelizumab also displayed a favorable pharmacokinetic(PK)and safety profile in cynomolgus monkeys.Besides,we showed that camrelizumab only bound to VEGFR2 with a very low affinity and did not activate VEGF pathways even at very high doses.Collectively,we provided evidence that cameralizumab was an ideal therapeutic candidate for cancer treatment,encouraging further evaluation of its efficacy/safety in the clinical setting.展开更多
文摘化学位移是核磁共振波谱(nuclear magnetic resonance spectrum,NMR)的一项重要参数,由于其对原子周围化学环境十分敏感,因此化学位移的理论计算在生物大分子的结构预测中扮演着重要的角色[1-2]。目前预测生物大分子NMR化学位移的理论方法主要分为两类:一类是从实验数据拟合得到的经验或者半经验方法[3-4];另一类是基于量子力学理论的从头计算方法[5-7]。与前者相比,量子力学方法不依赖数据集,针对不同体系具有很好的移植性。由于量子力学方法需要的计算时间随计算体系的大小呈多项式增长,因此人们基于“化学局域性”原理发展了分块量子化学方法来提高计算效率。本课题组长期致力于分块量子化学方法的发展,针对生物大分子的NMR化学位移精确预测发展了自动分块的大分子NMR化学位移计算方法(automated fragmentation,AF-NMR)。本文简要介绍本课题组在这方面的研究进展。
文摘Camrelizumab is a humanized monoclonal antibody(m Ab)against human PD-1.It demonstrated a single digit nanomolar binding affinity to human and cynomolgus monkey PD-1,but no cross-reactivity to murine PD-1.It exhibited potent PD-1/PD-L1 blocking activity as well as the T cell activation in vitro.The distinct binding sites of cameralizumab were perfectly overlapped with the PD-L1 binding sites,which supported its excellent ability in blocking PD-1/PD-L1 interaction.It also significantly inhibited the growth of murine MC-38 and B16 F10 cell in humanized PD-1 transgenic mice with a superior inhibitory effect compared with the other marketed anti-PD-1 antibodies.Furthermore,camrelizumab also displayed a favorable pharmacokinetic(PK)and safety profile in cynomolgus monkeys.Besides,we showed that camrelizumab only bound to VEGFR2 with a very low affinity and did not activate VEGF pathways even at very high doses.Collectively,we provided evidence that cameralizumab was an ideal therapeutic candidate for cancer treatment,encouraging further evaluation of its efficacy/safety in the clinical setting.
