Lactoferricin-related peptides with inhibitory effects on ACE-dependent vasoconstriction.
A selection of lactoferricin B (LfcinB)-related peptides with an angiotensin I-converting enzyme (ACE) inhibitory effect have been examined using in vitro and ex vivo functional assays. Peptides that were analyzed included a set of sequence-related antimicrobial hexapeptides previously reported and two representative LfcinB-derived peptides. In vitro assays using hippuryl-L-histidyl-L-leucine (HHL) and angiotensin I as substrates allowed us to select two hexapeptides, PACEI32 (Ac-RKWHFW-NH2) and PACEI34 (Ac-RKWLFW-NH2), and also a LfcinB-derived peptide, LfcinB17-31 (Ac-FKCRRWQWRMKKLGA-NH2). Ex vivo functional assays using rabbit carotid arterial segments showed PACEI32 (both D- and L-enantiomers) and LfcinB17-31 have inhibitory effects on ACE-dependent angiotensin I-induced contraction. None of the peptides exhibited in vitro ACE inhibitory activity using bradykinin as the substrate. In conclusion, three bioactive lactoferricin-related peptides exhibit inhibitory effects on both ACE activity and ACE-dependent vasoconstriction with potential to modulate hypertension that deserves further investigation.
Centeno
José M
JM
Departamento de Biotecnología de Alimentos, Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas, Burjassot, and Centro de Investigación, Hospital Universitario La Fe, Valencia, Spain.
Burguete
María C
MC
Castelló-Ruiz
María
M
Enrique
María
M
Vallés
Salvador
S
Salom
Juan B
JB
Torregrosa
Germán
G
Marcos
José F
JF
Alborch
Enrique
E
Manzanares
Paloma
P
D000803:Angiotensin I / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D017536:Carotid Artery, Common / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007781:Lactoferrin / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D010455:Peptides; C082171:lactoferricin B; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D007781:Lactoferrin