K A Ayub Nawaz1, Swapna Merlin David2, Easwaran Murugesh3, Murugesan Thandeeswaran1, Kalarikkal Gopikrishnan Kiran1, Ramasamy Mahendran1, Muthusamy Palaniswamy4, Jayaraman Angayarkanni5. 1. Department of Microbial Biotechnology, Bharathiar University, Coimbatore, Tamil Nadu 641 046, India. 2. Department of Biotechnology, Bharathiar University, Coimbatore, Tamil Nadu 641 046, India. 3. Department of Bioinformatics, Bharathiar University, Coimbatore, Tamil Nadu 641 046, India. 4. Department of Microbiology, Karpagam University, Coimbatore, Tamil Nadu 641 021, India. 5. Department of Microbial Biotechnology, Bharathiar University, Coimbatore, Tamil Nadu 641 046, India. Electronic address: angaibiotech@buc.edu.in.
Abstract
BACKGROUND: Plants are important sources of bioactive peptides. Among these, angiotensin converting enzyme (ACE) inhibitory peptides have a major focus on their ability to prevent hypertension. Inhibition of ACE has been established as an effective approach for the treatment of ACE associated diseases. HYPOTHESIS/ PURPOSE: Some synthetic ACE inhibitory drugs cause side effects and hence there is a constant interest in natural compounds as alternatives. STUDY DESIGN: The study was designed to identify and characterize a peptide molecule from pigeon pea which has the biological property to inhibit ACE and can be developed as a therapeutic approach towards hypertension. METHODS: Seeds of pigeon pea (Cajanus cajan (L.) Millsp.) was fermented with Aspergillus niger, a proteolytic fungus isolated from spoiled milk sweet. The extract was purified by size exclusion chromatography by FPLC system. The fractions that showed ACE inhibition was subjected to LC-MS/MS for sequence identification. The stability of the peptide was analyzed by molecular dynamic simulations and the interaction sites with ACE were identified by molecular docking. RESULTS: The study report a novel ACE inhibitory octapeptide Val-Val-Ser-Leu-Ser-Ile-Pro-Arg with a molecular mass of 869.53 Da. The Lineweaver-Burk plot indicated that the inhibition of ACE by this peptide is in competitive mode. Also, molecular docking and simulation studies showed a strong and stable interaction of the peptide with ACE. CONCLUSION: The results clearly show the inhibitory property of the peptide against ACE and hence it can be explored as a therapeutic strategy towards hypertension and other ACE associated diseases.
BACKGROUND: Plants are important sources of bioactive peptides. Among these, angiotensin converting enzyme (ACE) inhibitory peptides have a major focus on their ability to prevent hypertension. Inhibition of ACE has been established as an effective approach for the treatment of ACE associated diseases. HYPOTHESIS/ PURPOSE: Some synthetic ACE inhibitory drugs cause side effects and hence there is a constant interest in natural compounds as alternatives. STUDY DESIGN: The study was designed to identify and characterize a peptide molecule from pigeon pea which has the biological property to inhibit ACE and can be developed as a therapeutic approach towards hypertension. METHODS: Seeds of pigeon pea (Cajanus cajan (L.) Millsp.) was fermented with Aspergillus niger, a proteolytic fungus isolated from spoiled milk sweet. The extract was purified by size exclusion chromatography by FPLC system. The fractions that showed ACE inhibition was subjected to LC-MS/MS for sequence identification. The stability of the peptide was analyzed by molecular dynamic simulations and the interaction sites with ACE were identified by molecular docking. RESULTS: The study report a novel ACE inhibitory octapeptide Val-Val-Ser-Leu-Ser-Ile-Pro-Arg with a molecular mass of 869.53 Da. The Lineweaver-Burk plot indicated that the inhibition of ACE by this peptide is in competitive mode. Also, molecular docking and simulation studies showed a strong and stable interaction of the peptide with ACE. CONCLUSION: The results clearly show the inhibitory property of the peptide against ACE and hence it can be explored as a therapeutic strategy towards hypertension and other ACE associated diseases.