RESUMEN
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 869.53â¯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.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/química , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Cajanus/química , Péptidos/farmacología , Peptidil-Dipeptidasa A/química , Aspergillus niger/metabolismo , Cajanus/metabolismo , Dominio Catalítico , Cromatografía en Gel , Simulación por Computador , Evaluación Preclínica de Medicamentos/métodos , Humanos , Simulación del Acoplamiento Molecular , Peso Molecular , Péptidos/química , Péptidos/aislamiento & purificación , Peptidil-Dipeptidasa A/metabolismo , Espectrometría de Masas en TándemRESUMEN
Telomerase enzyme inhibitors have gained attention of scientific field due to the specificity of action of telomerase based therapies. Some telomerase have good combinatorial action with certain DNA damaging drugs. Natural compounds isolated from microbes provide a new scope of screening and large scale production of telomerase inhibitors. This review emphasizes the biochemistry and mode of action of different types of telomerase inhibitors isolated from microbial sources. Also elaborates on classification of telomerase inhibitors based on their mode of action in cancer cells.