Pharmacokinetic and Pharmacodynamic Profiles of Glyco-Modified Atrial Natriuretic Peptide Derivatives Synthesized Using Chemo-enzymatic Synthesis Approaches

Iwamoto Mitsuhiro; Yamaguchi Takahiro; Sekiguchi Yukiko; Oishi Shohei; Shiiki Takeshi; Soma Masako; Nakamura Kensuke; Yoshida Makoto; Chaya Hiroyuki; Mori Yutaka; Miyauchi Ryuki; Hasegawa Jun; Nagayama Takahiro; Honda Takeshi

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Pharmacokinetic and Pharmacodynamic Profiles of Glyco-Modified Atrial Natriuretic Peptide Derivatives Synthesized Using Chemo-enzymatic Synthesis Approaches

机译：使用化学酶合成方法合成的甘油改性心房利尿尿肽衍生物的药代动力学和药效谱

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Atrial natriuretic peptide (ANP) exerts beneficial pharmacological effects in the treatment of various cardiovascular disorders, such as acute congestive heart failure (ADHF). However, the clinical use of ANP is limited to the continuous intravenous infusion owing to its short half-life (2.4 +/- 0.7 min). In the present study, we conjugated the glyco-modified ANP with a monoclonal antibody (mAb) or an Fc via chemoenzymatic glyco-engineering using EndoS D233Q/Q303L. The most potent derivative SG-ANP-Fc conjugate half-life to 14.9 d and the duration of blood pressure lowering effect to over 28 d. This new biologic modality provides an opportunity to develop outpatient therapy after ADHF.

机译：心房钠尿肽（ANP）在治疗各种心血管障碍时施加有益的药理作用，例如急性充血性心力衰竭（ADHF）。然而，ANP的临床用途仅限于其短半衰期（2.4 +/- 0.7分钟）的连续静脉内输注。在本研究中，我们使用endoD D233 / Q303L通过化学酶组化学族聚糖 - 工程与单克隆抗体（MAb）或Fc将甘油改性的ANP与Fc缀合。最有效的衍生物SG-ANP-FC将半衰期缀合至14.9d，血压持续时间降低到超过28天。这种新的生物学模型提供了在ADHF后开发门诊治疗的机会。

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《Bioconjugate Chemistry》 |2018年第8期|共9页
作者
Iwamoto Mitsuhiro; Yamaguchi Takahiro; Sekiguchi Yukiko; Oishi Shohei; Shiiki Takeshi; Soma Masako; Nakamura Kensuke; Yoshida Makoto; Chaya Hiroyuki; Mori Yutaka; Miyauchi Ryuki; Hasegawa Jun; Nagayama Takahiro; Honda Takeshi;
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Daiichi Sankyo Co Ltd Sinagawa Ku 1-2-58 Hiromachi Tokyo 1408710 Japan;

Daiichi Sankyo Co Ltd Sinagawa Ku 1-2-58 Hiromachi Tokyo 1408710 Japan;

Daiichi Sankyo Co Ltd Sinagawa Ku 1-2-58 Hiromachi Tokyo 1408710 Japan;

Daiichi Sankyo Co Ltd Sinagawa Ku 1-2-58 Hiromachi Tokyo 1408710 Japan;

Daiichi Sankyo Co Ltd Sinagawa Ku 1-2-58 Hiromachi Tokyo 1408710 Japan;

Daiichi Sankyo Co Ltd Sinagawa Ku 1-2-58 Hiromachi Tokyo 1408710 Japan;

Daiichi Sankyo Co Ltd Sinagawa Ku 1-2-58 Hiromachi Tokyo 1408710 Japan;

Daiichi Sankyo Co Ltd Sinagawa Ku 1-2-58 Hiromachi Tokyo 1408710 Japan;

Daiichi Sankyo Co Ltd Sinagawa Ku 1-2-58 Hiromachi Tokyo 1408710 Japan;

Daiichi Sankyo Co Ltd Sinagawa Ku 1-2-58 Hiromachi Tokyo 1408710 Japan;

Daiichi Sankyo Co Ltd Sinagawa Ku 1-2-58 Hiromachi Tokyo 1408710 Japan;

Daiichi Sankyo Co Ltd Sinagawa Ku 1-2-58 Hiromachi Tokyo 1408710 Japan;

Daiichi Sankyo Co Ltd Sinagawa Ku 1-2-58 Hiromachi Tokyo 1408710 Japan;

Daiichi Sankyo Co Ltd Sinagawa Ku 1-2-58 Hiromachi Tokyo 1408710 Japan;

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正文语种 eng
中图分类生物化学;
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1. Pharmacokinetic and Pharmacodynamic Profiles of Glyco-Modified Atrial Natriuretic Peptide Derivatives Synthesized Using Chemo-enzymatic Synthesis Approaches [J] . Iwamoto Mitsuhiro, Yamaguchi Takahiro, Sekiguchi Yukiko, Bioconjugate Chemistry . 2018,第8期

机译：使用化学酶合成方法合成的甘油改性心房利尿尿肽衍生物的药代动力学和药效谱
2. Design and evaluation of novel natriuretic peptide derivatives with improved pharmacokinetic and pharmacodynamic properties [J] . Naomi Morozumi, Seiji Sato, Sayaka Yoshida, Peptides: An International Journal . 2017,第期

机译：具有改进的药代动力学和药学性质的新型利尿性肽衍生物的设计与评价
3. Atrial Natriuretic Peptide-Fc, ANP-Fc, Fusion Proteins: Semisynthesis, In Vitro Activity and Pharmacokinetics in Rats [J] . Adam R. Mezo, Kevin A McDonnell, Susan C. Low Bioconjugate Chemistry . 2012,第3期

机译：心钠素-Fc，ANP-Fc，融合蛋白：大鼠的半合成，体外活性和药代动力学
4. ATRIAL NATRIURETIC PEPTIDE (ANP); A CANDIDATE GENE FOR DEFORMITIES IN FISH? [C] . H. Takle, G. Basverfjord, O. Andersen International Conference of the European Aquaculture Society . 2004

机译：心房钠尿肽（ANP）;鱼类畸形的候选基因？
5. Atrial natriuretic peptide receptor subtype determination and biological actions of atrial natriuretic peptide in bovine cardiac muscle and hypertensive rat liver [D] . McCartney, Shirley. 1992

机译：心钠素受体亚型的测定及其在牛心肌和高血压大鼠肝脏中的作用
6. Vector synthesis high‐resolution electrocardiography atrial natriuretic peptide and N‐terminal prohormone brain natriuretic peptide for estimation of cardiac load in pregnancy [O] . Shino Tanaka, Rie Oyama, Akimune Fukushima, -1

机译：矢量合成高分辨率心电图心房利钠肽和N端激素激素钠对估计妊娠期心脏负荷的作用
7. Cellular mechanisms for synthesis and secretion of atrial natriuretic peptide and brain natriuretic peptide in cultured rat atrial cells. [O] . E Suzuki, Y Hirata, O Kohmoto, 1992

机译：培养大鼠心房细胞中心房利钠肽的合成和分泌细胞机制和脑利用肽。

Pharmacokinetic and Pharmacodynamic Profiles of Glyco-Modified Atrial Natriuretic Peptide Derivatives Synthesized Using Chemo-enzymatic Synthesis Approaches

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