1. Effects of some new angiotensin II analogs on the reactivity of small arterioles in the mesentery of rat intestine
J Folwarczna, W Janiec, L Sliwiński, R Paruszewski Pol J Pharmacol Pharm. 1989 Nov-Dec;41(6):585-9.
The influence of nine new angiotensin II analogs: Asp-Arg-Val-Tyr-Gly-His-Pro-Phe (1-RP), Asp-Arg-Val-DL-p-ClPhe-Ile-His-Pro-Phe (2-RP), epsilon Ahx-Arg-Val-Tyr-Ile-His-Pro-Phe (3-RP), Asp-Arg-Val-Tyr-beta Ala-His-Pro-Ile (4-RP), Asp-Arg-Val-Tyr-Ile-Pro-Phe (5-RP), beta Ala-Arg-Val-Tyr-D-Val-His-Pro-Lac (6-RP), beta Ala-Arg-Val-Tyr-Ile-His-Pro-Lac (7-RP), epsilon Ahx-Val-Tyr-Ile-His-Pro-Phe (8-RP) and Arg-Val-Tyr-Ile-His-Pro-Thr (9-RP) on the contractility of small arterioles in the rat intestinal mesentery was investigated. All the peptides had weaker contractile activity than angiotensinamide. The most potent new peptides presented 56% (1-RP), 67% (3-RP) and 78% (8-RP) of the agonistic activity of angiotensinamide. None of the new angiotensin II analogs had antagonistic activity. Compounds 1-RP and 3-RP presented the tendency to cause tachyphylaxis.
2. A specific binding site recognizing a fragment of angiotensin II in bovine adrenal cortex membranes
S G Bernier, A Fournier, G Guillemette Eur J Pharmacol. 1994 Dec 12;271(1):55-63. doi: 10.1016/0014-2999(94)90264-x.
We have characterized a specific binding site for angiotensin IV in bovine adrenal cortex membranes. Pseudo-equilibrium studies at 37 degrees C for 2 h have shown that this binding site recognizes angiotensin IV with a high affinity (Kd = 0.24 +/- 0.03 nM). The binding site is saturable and relatively abundant (maximal binding capacity around 0.5 pmol/mg protein). Non-equilibrium kinetic analyses at 37 degrees C revealed a calculated kinetic Kd of 47 pM. The binding site is pharmacologically distinct from the classic angiotensin receptors AT1 or AT2. Competitive binding studies with bovine adrenal cortex membranes demonstrated the following rank order of effectiveness: angiotensin IV (Val-Tyr-Ile-His-Pro-Phe) = angiotensin II-(3-7) (Val-Tyr-Ile-His-Pro) > angiotensin III (Arg-Val-Tyr-Ile-His-Pro-Phe) > or = angiotensin II-(4-7) (Tyr-Ile-His-Pro) > angiotensin II (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe) > angiotensin II-(1-6) (Asp-Arg-Val-Tyr-Ile-His) > angiotensin II-(4-8) (Tyr-Ile-His-Pro-Phe) > > > angiotensin II-(3-6) (Val-Tyr-Ile-His), angiotensin II-(4-6) (Tyr-Ile-His), L-158,809 (5,7-dimethyl-2-ethyl-3-[(2'(1-H-tetrazol-5-yl)[1,1'-biphenyl]-4-y l) methyl]-3-H-imidazo[4,5-beta]pyridine H2O) and PD 123319 (1-[4-(dimethylamino)3-methylphenyl]methyl-5-(diphenylacetyl)4,5,6 ,7- tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid). The divalent cations Mg2+ and Ca2+ were shown to diminish the binding of 125I-angiotensioffn IV to bovine adrenal cortex membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
3. Angiotensin II analogues with sulphur-containing side-chains in position 5. A structure-activity relationship study
J Pérodin, R Bouley, E Escher, N Assimomytis, V Magafa, E Manessi-Zoupa, D Theodoropoulos, P Cordopatis Arzneimittelforschung. 2000 Jun;50(6):526-9. doi: 10.1055/s-0031-1300242.
Four sets of angiotensin II (AngII) analogues with position 5 modifications, two agonist series with either Asp or Sar in position 1 and L-Phe in position 8, and two antagonist series with again Asp or Sar in position 1 and Leu in position 8 were synthesized. Modifications in positions 5 were introduced successively: Ile, Nle, Met, S-ethyl Cys, S-n-propyl-Cys, S-n-butyl Cys, S-t-butyl Cys and S-benzyl Cys in all four series. The study was undertaken in order to investigate the 5-position residue of AngII by replacing the hydrophobic side-chain by another containing an electrophilic moiety. The analogues were synthesised by solid phase synthesis using the Boc/Bzl or Fmoc/But strategy. All analogues were evaluated by their binding properties to the AT1 receptor on bovine adrenocortical membranes (bAT1). The results indicate that AngII analogues bind, irrespective of their agonistic or antagonistic nature or of their position 1 modification, in a similar manner and that position 5 modifications without beta-branching behave in an additive manner towards their affinity.
