Isolation of novel bioactive regions from bovine Achilles tendon collagen having angiotensin I-converting enzyme-inhibitory properties

被引:49
作者
Banerjee, Pradipta [1 ]
Shanthi, C. [1 ]
机构
[1] VIT Univ, Sch Bio Sci & Technol, Vellore 632014, Tamil Nadu, India
关键词
Bioactive peptide; ACE inhibition; Mechanistic action; Collagen; MUSCLE PROTEIN; PEPTIDES; ACE; ANTIOXIDANT; SITES; PURIFICATION; BINDING; ANGIOGENESIS; DEGRADATION; SELECTIVITY;
D O I
10.1016/j.procbio.2012.09.012
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Collagen, a structural biopolymer of the extracellular matrix, is known to conceal several bioactive peptides which, when excised, can display physiological actions including angiotensin II-converting enzyme (ACE) inhibition. ACE is a key protease controlling the blood pressure (BP) by cleaving dipeptides from an inactive propeptide to produce angiotensin II, a potent BP regulator. Natural inhibitors of ACE, though less potent, have the advantage of being biocompatible and non-toxic. This study was undertaken to identify such cryptic regions from bovine Achilles tendon collagen. Bacterial collagenase was used to hydrolyze collagen and the hydrolysate was subjected to separation through ion-exchange column chromatography. Fractions were subjected to ACE inhibition assays and further purified by gel permeation chromatography. Two biologically active cryptic peptides were obtained displaying potent inhibition abilities; D1 and E2. The peptides were in the mass range of 1.5-3.5 kDa and the inhibition was found to be competitive. Sequence analysis confirmed a relatively higher % occurrence of amino acids A and N in comparison to collagen and a hydrophobic C-terminal with P as the terminus. Both peptides were found to retain 80% of activity, even after digestive enzyme treatment. IC50 values revealed D1 to be the most potent inhibitor. Docking studies revealed that both peptides were using the C-terminal to interact with ACE-binding site. A comparison with other peptides displaying competitive inhibition hinted at the presence of a unique sequence GX'Y' where X' is often P, L, I or A and Y' often P as the probable C-terminal for effective inhibition. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:2335 / 2346
页数:12
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