Synthesis of a Novel PTH1–34 Analog with Increased Human Serum Albumin Affinity
| Autor: | Yuan-Zhen Dong, Jun Feng, Wei-Gen Lu, Lu Jianguang, Meng-Jia Zhao, Si-Da Ruan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
chemistry.chemical_classification
0303 health sciences Albumin Fatty acid Parathyroid hormone Peptide long-acting synthesis route Human serum albumin RS1-441 03 medical and health sciences 0302 clinical medicine Pharmacy and materia medica chemistry Biochemistry In vivo 030220 oncology & carcinogenesis medicine Potency pth1–34 analog fatty acid Receptor 030304 developmental biology medicine.drug |
| Zdroj: | Pharmaceutical Fronts, Vol 03, Iss 01, Pp e23-e29 (2021) |
| ISSN: | 2628-5096 2628-5088 |
| DOI: | 10.1055/s-0041-1731299 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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