Structural Requirements of Angiotensin I-Converting Enzyme Inhibitory Peptides: Quantitative Structure−Activity Relationship Study of Di- and Tripeptides

Citations Over TimeTop 10% of 2006 papers

Abstract

A database consisting of 168 dipeptides and 140 tripeptides was constructed from published literature to study the quantitative structure--activity relationships of angiotensin I-converting enzyme (ACE) inhibitory peptides. Two models were computed using partial least squares regression based on the three z-scores of 20 coded amino acids and further validated by cross-validation and permutation tests. The two-component model could explain 73.2% of the Y-variance (inhibitor concentration that reduced enzyme activity by 50%, IC50) with the predictive ability of 71.1% for dipeptides, while the single-component model could explain 47.1% of the Y-variance with the predictive ability of 43.3% for tripeptides. Amino acid residues with bulky side chains as well as hydrophobic side chains were preferred for dipeptides. For tripeptides, the most favorable residues for the carboxyl terminus were aromatic amino acids, while positively charged amino acids were preferred for the middle position, and hydrophobic amino acids were preferred for the amino terminus. According to the models, the IC50 values of seven new peptides with matchable primary sequences within pea protein, bovine milk protein, and soybean were predicted. The predicted peptides were synthesized, and their IC50 values were validated through laboratory determination of inhibition of ACE activity.

Related Papers

• → Simple Structural Requirements for Sequence-Selective Peptide Receptors? Tripeptide Binding by a Podand Ionophore(1997)14 cited
• → Systemic screening of milk protein-derived ACE inhibitors through a chemically synthesised tripeptide library(2011)10 cited
• Synthesis of the tripeptide L-Trp-L-Ser-L-Glu. Comparison of its biological activity with that of the delta-sleep-inducing-peptide (DSIP).(1977)
• → Synthesis of the ‘southern’ tripeptide of Cyclomarins A and C having novel anti-tuberculocidal mode of action(2011)6 cited
• → Copper Tripeptides(2022)