Transport of angiotensin peptides across the Caco-2 monolayer.
The bidirectional transport of the angiotensin peptides--des-Asp-angiotensin I (DAAI), angiotensins III and IV--were studied using human intestinal Caco-2 monolayers. The peptides had low permeability rates but were relatively stable to enzymatic hydrolysis. DAAI was transported by diffusion while angiotensins III and IV were transported by an energy requiring, carrier-mediated process. The physicochemical properties and solution conformations of the peptides were investigated in an attempt to establish structure-transport correlations. Among the three peptides, DAAI was the most hydrophobic, had the highest hydrogen bonding potential and was the only peptide to have a random solution conformation, as determined from circular dichroism, two-dimensional (1)H NMR and molecular modelling. On the other hand, the more hydrophilic angiotensin IV had less hydrogen bonding potential and a solution conformation characterized by a beta turn. These factors may influence the transport characteristics of DAAI and angiotensin IV.
Chua
Hui-Lee
HL
Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Jois
Seetharama
S
Sim
Meng-Kwoon
MK
Go
Mei-Lin
ML
D000803:Angiotensin I / Q000031:analogs & derivatives* / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000378:metabolism*; D000805:Angiotensin III / Q000378:metabolism*; D001693:Biological Transport, Active / Q000502:physiology; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D004058:Diffusion; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000804:Angiotensin II; D000805:Angiotensin III; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; C011437:angiotensin I, des-Asp(1)-; D000803:Angiotensin I