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CC BY 4.0 · Pharmaceutical Fronts 2021; 03(01): e23-e29
DOI: 10.1055/s-0041-1731299
Original Article

Synthesis of a Novel PTH1–34 Analog with Increased Human Serum Albumin Affinity

Si-Da Ruan
1   China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Yuan-Zhen Dong
1   China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Jian-Guang Lu
1   China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Meng-Jia Zhao
1   China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Wei-Gen Lu
1   China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Jun Feng
1   China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
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Abstract

Parathyroid hormone (PTH)1–34 is an effective peptide drug for osteoporosis therapy. However, the half-life of PTH1–34 in vivo is short, leading to the need for frequent injections of this drug during its treatment. To prolong the half-life of PTH1–34, a novel PTH1–34 analog was generated based on fatty acid generation, and its synthesis process included recombinant protein expression, side-chain modification, and peptide decoration. The PTH1–34 variant was expressed in Escherichia coli, with a single Lys (position 27) retained as a modification site. The side chain, –AEEA-γGlu-C18 diacid, was synthesized using 2-chlorotrityl chloride resin as a solid support, and then was conjugated to the PTH1-34 variant to form PTH-Lys27-AGC. Reversed-phase chromatography confirmed a high final purity (>98%) of the target compound; in vitro bioactivity tests showed that PTH-1 receptor potency of PTH-Lys27-AGC was comparable to that of the native PTH1–34. A competitive human serum albumin binding test demonstrated a high albumin affinity of PTH-Lys27-AGC in comparison to PTH1–34. In summary, we developed a novel PTH1–34 analog, PTH-Lys27-AGC, which may be a long-acting agent for osteoporosis treatment in the future.

Keywords

PTH1–34 analog - fatty acid - long-acting - synthesis route


Publikationsverlauf

Eingereicht: 02. April 2021

Angenommen: 28. Mai 2021

Artikel online veröffentlicht:
23. Juni 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
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