Total synthesis of human and rat coupling factor-6 amide and pressor effects in the rat.
Mitochondrial coupling factor-6 (CF-6) is a component of the ATP synthase complex essential for energy transduction. CF-6, which is localized to the surface of endothelial cells (ECs) and released by shear stress, has been implicated as an endogenous vasoconstrictor. Previous methods of obtaining CF-6 through purification and recombinant methods were laborious and inefficient. Here, we describe the chemical synthesis of human CF-6, (33-108)-NH(2), its C-terminal fragment (55-108)-NH(2), which is termed pCF-6; the rat CF-6, (33-108)-NH(2), its C-terminal fragment pCF-6, (55-108)-NH(2); and two N-terminal fragments of the rat pro-coupling factor-6, (24-52)-NH(2) and (33-52)-NH(2). Biological activities of each peptide were initially screened with bioassays and verified by in vivo studies. Accordingly, intravenous administration of CF-6, pCF-6, rat CF-6, and rat pCF-6 produced a modest but statistically significant increase in blood pressure and heart rate in urethane anesthetized rats, whereas the N-terminal rat pro-coupling factor-6, (24-52)-NH(2) and (33-52)-NH(2) caused no significant pressor response. Thus, the biologically active site probably resides at the C-terminal portion of CF-6 peptides.
Chang
J K
JK
Phoenix Pharmaceuticals, Inc, Belmont, CA, USA.
Scruggs
P
P
Yang
J
J
Ouyang
M
M
Duetzmann
A
A
Dun
N J
NJ
D000595:Amino Acid Sequence; D000758:Anesthesia; D018686:Anesthetics, Intravenous / Q000008:administration & dosage; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D024101:Mitochondrial Proteins / Q000138:chemical synthesis / Q000494:pharmacology; D025261:Mitochondrial Proton-Translocating ATPases / Q000138:chemical synthesis* / Q000494:pharmacology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010086:Oxidative Phosphorylation Coupling Factors / Q000138:chemical synthesis* / Q000494:pharmacology; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid; D014520:Urethane / Q000008:administration & dosage
D018686:Anesthetics, Intravenous; D024101:Mitochondrial Proteins; D010086:Oxidative Phosphorylation Coupling Factors; D010446:Peptide Fragments; D014520:Urethane; C000628217:F(6) ATPase; D025261:Mitochondrial Proton-Translocating ATPases; D011224:Prazosin