Size of the aliphatic chain of sodium houttuyfonate analogs determines their affinity for renin and angiotensin I converting enzyme.
Sodium houttuyfonate analogs (SHAs), CH(3)-(CH(2))(n)-CO-CH(2)-CH(OH)SO(3)Na, (n=6-14) were synthesized and their molecular interactions with renin and angiotensin I converting enzyme (ACE) studied using fluorescence quenching techniques. Unlike renin, inhibition of ACE activity was not directly proportional to the aliphatic chain length of SHAs. Ability of SHAs to inhibit enzyme activities and quench protein fluorescence was greater with renin than with ACE. The presence of an ACE substrate (angiotensin I) did not reduce quenching ability of SHAs, suggesting that enzyme-inhibitor interactions did not involve the active site or the substrate was displaced by inhibitor molecules. The results showed that renin is a more sensitive target than ACE for the potential antihypertensive ability of SHAs.
Yuan
Lujiang
L
Chemistry Institute of Pharmaceutical Resources, Southwest University, Chongqing 400716, People's Republic of China.
Wu
Jianping
J
Aluko
Rotimi E
RE
D000473:Alkanes / Q000737:chemistry*; D000803:Angiotensin I / Q000737:chemistry; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D000818:Animals; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry*; D011485:Protein Binding; D011817:Rabbits; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D012083:Renin / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013447:Sulfites / Q000737:chemistry*; D000092502:Renin Inhibitors
D000473:Alkanes; D000803:Angiotensin I; D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A; D011994:Recombinant Proteins; D012083:Renin; D013447:Sulfites; D000092502:Renin Inhibitors; C473296:sodium houttuyfonate