Characterization of Novel ACE-Inhibitory Peptides from <i>Nemopilema nomurai</i> Jellyfish Venom Hydrolysate: In Vitro and In Silico Approaches
The venom of <i>Nemopilema nomurai</i> jellyfish represents a promising source of bioactive compounds with potential pharmacological applications. In our previous work, we identified two novel angiotensin-converting enzyme (ACE)-inhibitory peptides—IVGRPLANG (896.48 Da) and IGDEPRHQYL (1...
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2025-06-01
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| author | Ramachandran Loganathan Mohan Prakash Deva Asirvatham Ravi Du Hyeon Hwang Changkeun Kang Euikyung Kim |
| author_facet | Ramachandran Loganathan Mohan Prakash Deva Asirvatham Ravi Du Hyeon Hwang Changkeun Kang Euikyung Kim |
| author_sort | Ramachandran Loganathan Mohan Prakash |
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| description | The venom of <i>Nemopilema nomurai</i> jellyfish represents a promising source of bioactive compounds with potential pharmacological applications. In our previous work, we identified two novel angiotensin-converting enzyme (ACE)-inhibitory peptides—IVGRPLANG (896.48 Da) and IGDEPRHQYL (1227.65 Da)—isolated from <i>N. nomurai</i> venom hydrolysates via papain digestion. In this study, we conducted a detailed biochemical and computational characterization of these peptides. The IC<sub>50</sub> values were determined to be 23.81 µM for IVGRPLANG and 5.68 µM for IGDEPRHQYL. Kinetic analysis using Lineweaver–Burk plots revealed that both peptides act as competitive ACE inhibitors, with calculated inhibition constants (K<sub>i</sub>) of 51.38 µM and 5.45 µM, respectively. To assess the structural stability of the ACE–peptide complexes, molecular dynamics simulations were performed. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analyses provided insights into complex stability, while interaction fraction analysis elucidated key bond types and residue–ligand contacts involved in binding. Furthermore, a network pharmacology approach was employed to predict therapeutic targets within the renin–angiotensin–aldosterone system (RAAS). Eleven target proteins were identified: IVGRPLANG was associated with REN, ACE, CTSB, CTSS, and AGTR2; IGDEPRHQYL was linked to REN, AGT, AGTR1, AGTR2, KNG1, and BDKR2. Molecular docking analyses using HADDOCK software (version 2.4) were conducted for all targets to evaluate binding affinities, providing further insight into the peptides’ therapeutic potential. |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-06-01 |
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| series | Marine Drugs |
| spelling | doaj-art-e324f2c276c449cea49db4777920d4302025-08-20T03:32:27ZengMDPI AGMarine Drugs1660-33972025-06-0123726710.3390/md23070267Characterization of Novel ACE-Inhibitory Peptides from <i>Nemopilema nomurai</i> Jellyfish Venom Hydrolysate: In Vitro and In Silico ApproachesRamachandran Loganathan Mohan Prakash0Deva Asirvatham Ravi1Du Hyeon Hwang2Changkeun Kang3Euikyung Kim4College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Republic of KoreaCollege of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Republic of KoreaCollege of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Republic of KoreaCollege of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Republic of KoreaCollege of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Republic of KoreaThe venom of <i>Nemopilema nomurai</i> jellyfish represents a promising source of bioactive compounds with potential pharmacological applications. In our previous work, we identified two novel angiotensin-converting enzyme (ACE)-inhibitory peptides—IVGRPLANG (896.48 Da) and IGDEPRHQYL (1227.65 Da)—isolated from <i>N. nomurai</i> venom hydrolysates via papain digestion. In this study, we conducted a detailed biochemical and computational characterization of these peptides. The IC<sub>50</sub> values were determined to be 23.81 µM for IVGRPLANG and 5.68 µM for IGDEPRHQYL. Kinetic analysis using Lineweaver–Burk plots revealed that both peptides act as competitive ACE inhibitors, with calculated inhibition constants (K<sub>i</sub>) of 51.38 µM and 5.45 µM, respectively. To assess the structural stability of the ACE–peptide complexes, molecular dynamics simulations were performed. Root mean square deviation (RMSD) and root mean square fluctuation (RMSF) analyses provided insights into complex stability, while interaction fraction analysis elucidated key bond types and residue–ligand contacts involved in binding. Furthermore, a network pharmacology approach was employed to predict therapeutic targets within the renin–angiotensin–aldosterone system (RAAS). Eleven target proteins were identified: IVGRPLANG was associated with REN, ACE, CTSB, CTSS, and AGTR2; IGDEPRHQYL was linked to REN, AGT, AGTR1, AGTR2, KNG1, and BDKR2. Molecular docking analyses using HADDOCK software (version 2.4) were conducted for all targets to evaluate binding affinities, providing further insight into the peptides’ therapeutic potential.https://www.mdpi.com/1660-3397/23/7/267angiotensin-converting enzyme inhibitorspeptide characterizationLineweaver–Burk plotmolecular docking and dynamicsnetwork pharmacology |
| spellingShingle | Ramachandran Loganathan Mohan Prakash Deva Asirvatham Ravi Du Hyeon Hwang Changkeun Kang Euikyung Kim Characterization of Novel ACE-Inhibitory Peptides from <i>Nemopilema nomurai</i> Jellyfish Venom Hydrolysate: In Vitro and In Silico Approaches Marine Drugs angiotensin-converting enzyme inhibitors peptide characterization Lineweaver–Burk plot molecular docking and dynamics network pharmacology |
| title | Characterization of Novel ACE-Inhibitory Peptides from <i>Nemopilema nomurai</i> Jellyfish Venom Hydrolysate: In Vitro and In Silico Approaches |
| title_full | Characterization of Novel ACE-Inhibitory Peptides from <i>Nemopilema nomurai</i> Jellyfish Venom Hydrolysate: In Vitro and In Silico Approaches |
| title_fullStr | Characterization of Novel ACE-Inhibitory Peptides from <i>Nemopilema nomurai</i> Jellyfish Venom Hydrolysate: In Vitro and In Silico Approaches |
| title_full_unstemmed | Characterization of Novel ACE-Inhibitory Peptides from <i>Nemopilema nomurai</i> Jellyfish Venom Hydrolysate: In Vitro and In Silico Approaches |
| title_short | Characterization of Novel ACE-Inhibitory Peptides from <i>Nemopilema nomurai</i> Jellyfish Venom Hydrolysate: In Vitro and In Silico Approaches |
| title_sort | characterization of novel ace inhibitory peptides from i nemopilema nomurai i jellyfish venom hydrolysate in vitro and in silico approaches |
| topic | angiotensin-converting enzyme inhibitors peptide characterization Lineweaver–Burk plot molecular docking and dynamics network pharmacology |
| url | https://www.mdpi.com/1660-3397/23/7/267 |
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