Angiotensin converting enzyme and nitric oxide inhibitory activities of novel milk derived peptides

This study used bioinformatics to mine the five major milk proteins for angiotensin converting enzyme- (ACE-) inhibitor peptides. We found three ACE-inhibitors, two of which were novel (QSWMHQPHQ and YYAKPAAVR). Peptides QSWMHQPHQ and YYAKPAAVR dose-dependently increased ACE inhibition with IC50 values of 19.26 and 48.88 μm, respectively. RAW 264.7 cells were subsequently stimulated with lipopolysaccharide (LPS) to determine if these peptides also affected nitric oxide synthesis. We showed that YYAKPAAVR dose-dependently inhibited nitrite accumulation in LPS stimulated RAW 264.7 cells. We found that QSWMHQPHQ inhibited nitric oxide accumulation at 100 μm. Our results indicate that peptides on their own or in the presence of LPS had no significant effect on cell viability. Hence, this inhibition of nitric oxide accumulation was not due to a potential cytotoxic effect of the peptides. Bioinformatics may be used to identify additional novel peptides with multifunctional bioactivity.