title: Tryptophan-containing dipeptides are C-domain selective inhibitors of angiotensin converting enzyme.
abstract: Somatic angiotensin-converting enzyme (ACE) contains two active sites, the C- and N-domain, from which the C-domain is supposed to play a major role in blood pressure regulation and is therefore a promising pharmacological target to reduce blood pressure without side-effects. We report for the first time that tryptophan-containing dipeptides such as Ile-Trp or Val-Trp, which were recently found in food protein hydrolysates, are selective and competitive inhibitors for the C-domain with a selectivity factor of 40 and 70, respectively. Structure-activity studies showed that an N-terminal aliphatic amino acid and a tryptophan moiety in the P2' position are favourable structures for C-domain inhibition in dipeptides. In contrast, the lactotripeptides Ile-Pro-Pro and Val-Pro-Pro, which were widely used as ingredients for hypotensive food, showed a slight selectivity for the N-domain. Hence, tryptophan containing dipeptides are interesting ingredients for functional foods as a natural prevention for hypertension with reduced side effects due to its selective inhibition of the C-domain.
authors: Institute of Food Chemistry, Technische Universität Dresden, D-01062 Dresden, Germany.
authors: Diana
authors: D
authors: Lunow
authors: Institute of Food Chemistry, Technische Universität Dresden, D-01062 Dresden, Germany.
authors: Susanne
authors: S
authors: Kaiser
authors: Institute of Food Chemistry, Technische Universität Dresden, D-01062 Dresden, Germany.
authors: Jana
authors: J
authors: Rückriemen
authors: Institute of Food Chemistry, Technische Universität Dresden, D-01062 Dresden, Germany.
authors: Christoph
authors: C
authors: Pohl
authors: Institute of Food Chemistry, Technische Universität Dresden, D-01062 Dresden, Germany. Electronic address: Thomas.Henle@chemie.tu-dresden.de.
authors: Thomas
authors: T
authors: Henle
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D020134:Catalytic Domain; D004151:Dipeptides / Q000737:chemistry; D006801:Humans; D006973:Hypertension / Q000517:prevention & control; D009842:Oligopeptides / Q000737:chemistry; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry; D011492:Protein Hydrolysates / Q000737:chemistry; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; D009842:Oligopeptides; D011492:Protein Hydrolysates; C489032:isoleucyl-prolyl-proline; C489031:valyl-prolyl-proline; C055060:N-valyltryptophan; D014364:Tryptophan; D007703:Peptidyl-Dipeptidase A
keywords: Angiotensin converting enzyme (ACE); Bioactive peptides; Domain selective inhibitors; Tryptophan peptides