The Chemistry and Pharmacology of Angiotensin

Schwyzer, R.; Turrian, H

doi:10.1016/s0083-6729(08)60864-x

Cited by 46 publications

(5 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No significant difference was observed between the EC 50 value for [ n ‐Leu 5 ]AII and that for analogs in which a sulfur atom, such as [Met 5 ]AII or [Cys(S‐tert butyl) 5 ]AII, was inserted without β‐branching, except for the affinity of the analog [Cys(S‐propy) 5 ]AII, which was much lower than that of the other analogs (Table 1). The finding that replacement of Ile 5 by n ‐Leu caused a significant reduction in the relative affinity to AII, which can be ascribed to the lack of β‐branching, is in agreement with the results reported by Schwyzer and Turrian (9) and Khosla et al . (10) regarding the pressor activity.…”

Section: Resultssupporting

confidence: 93%

Insertion of an electronegative sulfur atom in the side chain of position 5 of angiotensin II: changes in the tachyphylactic properties of the peptide

Zalcberg

Assimomytis

Magafa

et al. 1999

The Journal of Peptide Research

View full text Add to dashboard Cite

Angiotensin II (AII) analogs bearing n-Leu, Met or S-substituted groups for cysteine at position 5 were studied regarding their agonistic and tachyphylactic properties. It was shown that these analogs lowered the relative affinity towards the AT1 receptor as determined by contractile responses, which could be due to the removal of the beta-branching residue at position 5. Insertion of a sulfur atom in a different position away from the attached backbone carbon atom presented no significant difference in EC50 values for these analogs. Interestingly, the S-bearing analogs at position 5 were full agonists but the tachyphylactic property was lost, in contrast to [n-Leu5]AII, which still induced reduction of the contractile responses. Nevertheless after replacing the Asp with Sar in position 1 (Sar1) tachyphylaxis was again established. It is concluded that the insertion of Met or an S-substituted cysteine into the side chain at position 5 of AII may promote interactions with its receptor due to the slight electronegative character of the sulfur atom and changes in the restricted conformational freedom of the Ile5 residue in the AII molecule. This was overcome by Sar1, probably through interactions due to its fully protonated N-terminal amino group and favoring the conformation responsible for the tachyphylaxis phenomenon.

show abstract

Section: Resultssupporting

confidence: 93%

Insertion of an electronegative sulfur atom in the side chain of position 5 of angiotensin II: changes in the tachyphylactic properties of the peptide

Zalcberg

Assimomytis

Magafa

et al. 1999

The Journal of Peptide Research

View full text Add to dashboard Cite

show abstract

“…These can be correlated with the calculated steric parameter V.y (Table 1 and There is considerable evidence suggesting that the carboxyl group of All is involved in the binding process, since suppression, sequential positional shift, amidation, or change of configuration destroy or greatly reduce the biological activity (18,19). The present conformational study indicates that in All the free carboxyl group is subjected to specific steric restriction by the aromatic side chain of phenylalanine.…”

mentioning

confidence: 52%

“…For instance, amidation of the carboxyl group in the hormone simultaneously alters the side chain organization (Jaw and Jan' = 5.5 and 8.4 Hz in All versus 5.0 and 8.7 Hz in All amide) and the backbone conformation (3J CHa-NH = +0.5 Hz), while effects are very weak or null when position 8 is occupied by isoleucine or glycine (Table 1). However, direct information on the carboxyl spatial orientation is not available and one assumes that variations of 3J HCar-NH reflect connected changes of 4 and q, since these two angles are interdependent (19)(20)(21)(22)(23). This holds (Fig.…”

mentioning

confidence: 99%

Studies on angiotensin II and analogs: impact of substitution in position 8 on conformation and activity.

Aumelas¹,

Sakarellos²,

Lintner³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Affinity, residual agonist activity, and inhibitor properties of a series of angiotensin II analogs modified at the COOH-terminal position (X8-substituted peptides) have been probed for structure/conformation-biological activity relationships. The results emphasize (t) the large impact that subtle conformational variations caused by structural alterations in the position 8 side chain have on biological properties, (it) the implication of the COOH-terminal carboxyl group in both affinity and intrinsic activity, and (Wi) the influence that the bulkiness of the side chain in position 8 of antagonists has on the local conformation at the COOH terminus and thus on the inhibitory properties. In the hormone, the phenylalanine-8 ring is required for its steric influence and aromaticity to ensure a fully active conformation at the COOH terminus. Especially, correct orientation of the position 8 carboxyl group relative to the phenyl group of the phenylalanine residue may be necessary for agonistic activation of the angiotensin receptor complex. Replacement of the aromatic ring on the COOHterminal residue by a nonaromatic group leads to incorrect orientation of the carboxyl group and causes the appearance of antagonist properties. Although the steric effects of the side chain can be modulated by specific interaction of its chemical groups (if any) with the peptide backbone, we found a good correlation between the size of the side chain-e.g., the steric parameter Vy (the van der Waals volume consisting of the C., Cp, and Cy atoms), the conformational properties in the backbone (3J HC.t-NH), and the binding capacities in all compounds tested.

show abstract

“…The AII effects were the result of infusion of a form of the peptide not produced biologically in any species (23). Although the qualitative effects of Asn-1, Val-5 AII have been reported identical to endogenously produced AII (24,25), it remains possible that these results were unique to this synthetic form of AI. For these reasons, studies were performed with Asp-1, Ile-5 AII, the form of AII produced by the rat (13).…”

Section: Resultsmentioning

confidence: 99%

Angiotensin II effects upon the glomerular microcirculation and ultrafiltration coefficient of the rat.

Blantz¹,

Konnen²,

Tucker³

1976

J. Clin. Invest.

398

159

View full text Add to dashboard Cite

A B S T R A CT The effects of both synthetic and biologically produced angiotensin II (AII) upon the process of glomerular filtration were examined in the plasma-expanded (2.5% body wt) Munich-Wistar rat, by micropuncture evaluation of pressures, nephron plasma flow (rpf) and filtration rate (sngfr). Plasma expansion was chosen as a control condition because (a) response to AII was uniform and predictable, (b) endogenous generation of AII was presumably suppressed, and (c) the high control values for rpf permitted accurate determination of values for the glomerular permeability coefficient (LPA) before and during AII infusion. With subpressor quantities of synthetic Asn-1, Val-5 AII (< 5 ng/100 g body wt/min), sngfr fell from 47.7 in the control group to 39.8 nl/min/g kidney (P < 0.005). The rpf fell to 60% of control values (P < 0.001). Measurement of glomerular capillary (Pa) and Bowman's space (P.) hydrostatic pressures in surface glomeruli with a servo-nulling device permitted evaluation of the hydrostatic pressure gradient (AP = Pa-P0). AP increased from 38.1+±1.2 in control to 45.9±1.3 mm Hg after Asn-1, Val-5 AII and essentially neutralized the effect of decreased rpf in sngfr. The sngfr then fell as a result of a decrease in LPA from 0.063+0.008 in control to 0.028±0.004 nl/s/g kidney/mm Hg after Asn-1, Val-5 AII (P < 0.02).Lower doses of Asp-1, Ile-5 AII (< 3 ng/100 g body wt/min) had no effect on sngfr, rpf, AP, and afferent and efferent vascular resistance, but significantly elevated systemic blood pressure, suggesting peripheral ef- fects on smooth muscle at this low dose. LPA was 0.044+ 0.007 nl/s/g kidney/mm Hg after low-dose Asp-1, Ile-5 AII, and 0.063±0.008 in the control group (0.2 > P > 0.1). Higher, equally pressor doses of native AII (5 ng/ 100 g body wt/min) produced effects almost identical to similar quantites of synthetic Asn-1, Val-5 AII upon rpf, AP, sngfr, and renal vascular resistance. LPA again fell to 0.026±0.004 nl/s/g kidney/mm Hg, a value almost identical to that after the synthetic AI. Paired studies with Asp-1, Ile-5 AII also demonstrated a consistent reduction in LPA.Both synthetic (Asn-1, Val-5 AII) and native AII (Asp-1, Ile-5 AII) produce a reduction in LpA, presumably by direct action on the glomerular capillary or mesangium, where no smooth muscle cells are present. Although quantitative differences in peripheral vascular effects of the two forms of AII are demonstrated, the effects on LPA occur at similar doses of both agents in the plasma-expanded rat. A third major physiologic action for AII is postulated that requires an effector cell in the glomerulus that differs from those previously demonstrated for vascular smooth muscle and the adrenal glomerulosa.

show abstract

The Chemistry and Pharmacology of Angiotensin

Cited by 46 publications

References 93 publications

Insertion of an electronegative sulfur atom in the side chain of position 5 of angiotensin II: changes in the tachyphylactic properties of the peptide

Insertion of an electronegative sulfur atom in the side chain of position 5 of angiotensin II: changes in the tachyphylactic properties of the peptide

Studies on angiotensin II and analogs: impact of substitution in position 8 on conformation and activity.

Angiotensin II effects upon the glomerular microcirculation and ultrafiltration coefficient of the rat.

Contact Info

Product

Resources

About