title: Myristic acid-modified thymopentin for enhanced plasma stability and immune-modulating activity.
abstract: Natural albumin ligand (fatty acids)-conjugated peptides can rapidly bind to circulating albumin and form complexes to control the release of peptides. The purpose of this study was to prolong the half-life and immune-modulating effects of thymopentin (TP5) by using the albumin binding strategy. We synthesized myristic acid-modified TP5 (TP5-MA) by conjugating a myristic acid-acylated lysine to a permissive site of TP5, which improved the albumin binding affinity of TP5-MA and dramatically enhanced its stability in human plasma. We observed well-preserved bioactivities of TP5-MA in RAW264.7 macrophages using a tumor necrosis factor (TNF)-α stimulation assay. Moreover, the prolonged immune-modulating effect of TP5-MA was confirmed by the normalized CD4+/CD8+ratio in immune-depressed rat models, which resulted in a reduced administration frequency (twice per week). In general, the enhanced pharmacokinetic and pharmacodynamic properties of TP5-MA make it a promising product for the treatment of immunodeficiency diseases.
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
authors.forename: Yuanyan
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Wu
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Zhengyin
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Guiyang
authors.initials: G
authors.lastname: Yao
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Fang
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China. Electronic address: wu.su@siat.ac.cn.
authors.forename: Wu
authors.initials: W
authors.lastname: Su
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D016516:CD4-CD8 Ratio; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007153:Immunologic Deficiency Syndromes / Q000276:immunology / Q000628:therapy*; D056747:Immunomodulation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019814:Myristic Acid / Q000737:chemistry; D011485:Protein Binding; D055550:Protein Stability; D000067996:RAW 264.7 Cells; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D016305:Thymopentin / Q000737:chemistry / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D019814:Myristic Acid; D016305:Thymopentin
keywords: Albumin binding affinity; Immune-modulating effects; Myristic acid; Plasma stability; Thymopentin (TP5)