Properties of ACE inhibitory peptides isolated from Sipunculus nudus L and a DSPE-PEG modification for sustained release anti-hypertension agent. (April 2023)

• Record Type: Journal Article
• Authors: Cai, Xiaoxuan; Huang, Miaoen; Huang, Xixiang; Liu, Huan; Wang, Tianji; Li, Li; Yang, Weiguang; Luo, Hui; Lu, Yingnian
• Is Part Of: Process biochemistry. Volume 127(2023)
• Page Start: 56
• Page End: 65
• Publication Date: 2023-04
• Subjects: RAS renin-angiotensin-aldosterone system -- ACEI angiotensin I converting enzyme inhibitory -- DSPE 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine -- PEG polyethylene glycol -- DSPE-PEG-NHS, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[hydroxysuccinimidyl(polyethylene glycol)− 2000] -- NHS, Succinimide -- TOF, Time of Flighty -- VSMC, vascular smooth muscle -- HHL, hippuryl-histidine-leucine -- HA, hippuric acid -- FTIR, Fourier Transform infrared spectroscopy -- TLC, thin-layer chromatography; Sipunculus nudus L -- ACE activity -- Tripeptide -- PEG modification -- Drug sustained release; Biochemical engineering -- Periodicals; Biotechnology -- Periodicals; Biochemistry -- periodicals; Biotechnology -- periodicals; Chemical Engineering -- periodicals; Génie biochimique -- Périodiques; Biotechnologie -- Périodiques; Biochemical engineering; Biotechnology; Periodicals; 660.63
• DOI: 10.1016/j.procbio.2023.02.003
• Languages: English
• ISSNs: 1359-5113

Abstract

Abstract: The organism Sipunculus nudus L is a good resource for marine peptides because of its rich protein. However, the disadvantage of biological peptides is their short metabolic half-life, therefore, structural modification of peptides is necessary. In this research, the enzymatic hydrolysis of Sipunculus nudus L was performed using trypsin and then peptides were isolated and purified from the hydrolysates, four novel tripeptides were identified by LC-MS-MS as Ser-Arg-Pro (SRP, m/z = 358.39), Pro-Arg-Pro (PRP, m/z = 368.43), Arg-Pro-Ala (RPA, m/z = 342.39), and Lue-Pro-Lys (LPK, m/z = 356.46), their ACE inhibitory activity was investigated with IC50 value as following 0.046, 0.42, 0.97, and 6.54 mM, respectively. Because of its highest ACE inhibitory activity, SRP was further selected to modify the chemical structure for a sustained release agent DSPE-PEG-SRP. Compared with 7 h of free SRP, the release of DSPE-PEG-SRP in vitro was approximately 120 h. The ACE inhibition rate of SRP released from the synthetic product and the raw material SRP was almost the same, molecular docking demonstrated that ACE inhibitory activity was attributed to the formation of hydrogen bonds between SRP and ACE active sites. In conclusion, DSPE-PEG-SRP, a novel sustained release agent, has great potential and is expected to be further applied to treat hypertension. Graphical Abstract: ga1 Highlights: Novel tripeptides were identified from Sipunculus nudus L as Ser-Arg-Pro (SRP), Lue-Pro-Lys (LPK), Pro-Arg-Pro (PRP), Arg-Pro-Ala (RPA). The IC50 value of Ser-Arg-Pro (SRP) was the lowest as 0.046 mM. A long-acting molecular DSPE-PEG-SRP was achieved with yield 45%. The release of DSPE-PEG-SRP in vitro was 120 h, whereas that only 7 h of SRP.