Systematical mutational analysis of teriparatide on anti-osteoporosis activity by alanine scanning.
Bioorg Med Chem Lett
; 104: 129732, 2024 May 15.
Article
em En
| MEDLINE
| ID: mdl-38583785
ABSTRACT
Osteoporosis is a progressive systemic skeletal disease that decreases bone density and bone quality, making them fragile and easy to break. In spite of effective anti-osteoporosis potency, teriparatide, the first anabolic medications approved for the treatment of osteoporosis, was proven to exhibit various side effects. And the relevant structure-activity relationship (SAR) of teriparatide was in need. In this work, we performed a systematical alanine scanning against teriparatide and synthesized 34 teriparatide derivatives. Their biological activities were evaluated and the importance of each residue for anti-osteoporosis activity was also revealed. A remarkable decrease in activity was observed for alanine replacement of the residue Gly12, His14, Ser17, Arg20 and Leu24, showcasing the important role of these residues in teriparatide on anti-osteoporosis activity. On contrary, when Gly13 and Gln30 were mutated to Ala, the peptide derivatives exhibited the significantly increased activities, demonstrating that these two residues could be readily replaced. Our research expanded the peptide library of teriparatide analogues and presented a potential opportunity for designing the more powerful anti-osteoporosis peptide agents.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteoporose
/
Teriparatida
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Conservadores da Densidade Óssea
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article