Essential of proline and valine residues in the peptide derived from lactoferrin for angiotensin converting enzyme inhibition

摘要

We synthesized Leu-Arg-Pro-Val-Ala-Ala-Glu, the peptide contained in lactoferrin (Lf), to identify the angiotensin converting enzyme (ACE) inhibition. In an attempt to know the structure-activity relationship of this peptide, we replaced Pro (the third amino acid residues from N-terminal) or Val (the fourth amino acid residues from N-terminal) with Ala (neutral amino acid), Glu (acidic amino acid) or Lys (basic amino acid) to produce six peptides. From the in vitro ACE inhibition (IC50) of these synthesized peptides, the original peptide (Leu-Arg-Pro-Val-Ala-Ala-Glu) showed higher ACE inhibition than the replaced six peptides. Thus, replacement of Pro at the third amino acid residues or Val at the fourth position with Ala, Glu or Lys revealed the ACE inhibition to be lower than the original form of Leu-Arg-Pro-Val-Ala-Ala-Glu. Otherwise, we added one peptide at the C-terminal of Leu-Arg-Pro-Val-Ala-Ala-Glu and found both products with an addition of Val (Leu-Arg-Pro-Val-Ala-Ala-Glu-Val) or Ile (Leu-Arg-Pro-Val-Ala-Ala-Glu-Ile) showing a lower ACE inhibition than the original one. The ACE inhibitions produced by both replaced peptides were without significance. Also, deletion of the last peptide at the C-terminal (Leu-Arg-Pro-Val-Ala-Ala) failed to produce a marked change of ACE inhibition as compared to the original one. These results suggest that Pro and Val are essential in the peptide for inhibition of ACE activity.