A proopiomelanocortin-derived peptide sequence enhances plasma stability of peptide drugs.
FEBS LETTERS(2020)
摘要
Bioactive peptide drugs hold promise for therapeutic application due to their high potency and selectivity but display short plasma half-life. Examination of selected naturally occurring peptide hormones derived from proteolytic cleavage of the proopiomelanocortin (POMC) precursor lead to the identification of significant plasma-stabilizing properties of a 12-amino acid serine-rich orphan sequence NSSSSGSSGAGQ in human gamma 3-melanocyte-stimulating hormone (MSH) that is homologous to previously discovered NS(n)GGH (n = 4-24) sequences in owls. Notably, transfer of this sequence to des-acetyl-alpha-MSH and the therapeutically relevant peptide hormones neurotensin and glucagon-like peptide-1 likewise enhance their plasma stability without affecting receptor signaling. The stabilizing effect of the sequence module is independent of plasma components, suggesting a direct effect incis. This natural sequence module may provide a possible strategy to enhance plasma stability, complementing existing methods of chemical modification.
更多查看译文
关键词
blood plasma,cerebrospinal fluid,peptide-drug stabilization,gamma 3-MSH-derived tag
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要