Novel Antihypertensive Lactoferrin-Derived Peptides Produced by Kluyveromyces marxianus

Novel antihypertensive peptides released by Kluyveromyces marxianus from bovine lactoferrin (LF) have been identified. K. marxianus LF permeate was fractionated by semipreparative high performance liquid chromatography and 35 peptides contained in the angiotensin I-converting enzyme (ACE)-inhibitory fractions were identified by using an ion trap mass spectrometer. On the basis of peptide abundance and common structural features, six peptides were chemically synthesized. Four of them (DPYKLRP, PYKLRP, YKLRP, and GILRP) exerted in vitro inhibitory effects on ACE activity and effectively decreased systolic blood pressure after oral administration to spontaneously hypertensive rats (SHRs). Stability against gastrointestinal enzymes suggested that the sequence LRP could contribute to the in vivo effects of parental peptides. Finally, there were reductions in circulating ACE activity and angiotensin II level in SHRs after either DPYKLRP or LRP intake, thus confirming ACE inhibition as the in vivo mechanism for their antihypertensive effect.This work was supported by grant AGL2010–21009 from ‘Ministerio de Educación y Ciencia - FEDER’, Consolider Ingenio 2010, Fun-C-Food, CSD2007–00063 and RETICS INVICTUS RD12/0014/0004 from ‘Instituto de Salud Carlos III’. A.G.-T. is the recipient of a predoctoral fellowship from ‘Ministerio de Educación y Ciencia’ (BES-2011–044424).Peer reviewe