CAS Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
Lab for Marine Biology and Biotechnology, Qingdao National Lab for Marine Sci. & Tech, Qingdao 266071, China.
Mar Drugs. 2018 Aug 27;16(9):299. doi: 10.3390/md16090299.
A variety of biologically active products have been isolated from . In the present study, two novel angiotensin-converting enzyme (ACE) inhibitory peptides, FQIN [M(O)] CILR, and TGAPCR, were screened and identified from protein hydrolysates by LC-MS/MS. The IC50 values of FQIN [M(O)] CILR and TGAPCR were 9.64 ± 0.36 μM and 23.94 ± 0.82 μM, respectively. In the stability study, both peptides showed stabilities of pH, temperature, simulated gastrointestinal digestion, and ACE hydrolysis. The Lineweaver⁻Burk plot showed that the two peptides were noncompetitive inhibitors of ACE. Molecular docking simulated the intermolecular interactions of two peptides and ACE, and the two peptides formed hydrogen bonds with the active pockets of ACE. However, FQIN [M(O)] CILR was more closely linked to the active pockets of ACE, thereby exerting better ACE inhibition. Spontaneously hypertensive rats (SHRs) were studied with an oral dose of 10 mg/kg body weight. Both peptides reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) in SHRs, of which FQIN [M(O)] CILR was able to reduce the systolic blood pressure by 34 mmHg (SBP) ( < 0.05). Therefore, FQIN [M(O)] CILR was an excellent ACE inhibitory peptide.
从 中分离得到了多种具有生物活性的产物。在本研究中，通过 LC-MS/MS 从 蛋白水解物中筛选并鉴定出两种新型血管紧张素转化酶（ACE）抑制肽 FQIN[M(O)]CILR 和 TGAPCR。FQIN[M(O)]CILR 和 TGAPCR 的 IC50 值分别为 9.64±0.36 μM 和 23.94±0.82 μM。在稳定性研究中，两种肽均表现出对 pH、温度、模拟胃肠道消化和 ACE 水解的稳定性。Lineweaver-Burk 作图表明，这两种肽均为 ACE 的非竞争性抑制剂。分子对接模拟了两种肽与 ACE 之间的分子间相互作用，两种肽均与 ACE 的活性口袋形成氢键。然而，FQIN[M(O)]CILR 与 ACE 的活性口袋结合更紧密，从而发挥更好的 ACE 抑制作用。采用 10 mg/kg 体重的口服剂量对自发性高血压大鼠（SHR）进行研究。两种肽均降低 SHR 的收缩压（SBP）和舒张压（DBP），其中 FQIN[M(O)]CILR 可使 SBP 降低 34 mmHg（SBP）（<0.05）。因此，FQIN[M(O)]CILR 是一种优秀的 ACE 抑制肽。
