Synthesis and pharmacological properties of TOAC-labeled angiotensin and bradykinin analogs

Nakaie, Clóvis R.; Silva, E. G.; Cilli, Eduardo Maffud; Marchetto, Reinaldo; Schreier, Shirley; Paiva, Therezinha B.; Paiva, A. C. M.

doi:10.1016/s0196-9781(01)00580-0

Cited by 44 publications

(50 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, we were also able to discriminate differences between ligand specificities for ACE or AT 1 by using the TOAC 3 -Ang II derivative, where TOAC (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) is a spin-labeled amino acid that was internally coupled to Ang II. 21 TOAC 3 -Ang II, which is not able to bind or activate AT 1 receptors, 11,14 could stimulate CHO-ACE cells, increasing intracellular Ca 2ϩ , again suggesting a specific calcium signaling by ACE. In addition, we could demonstrate that the effect was specific for Ang II, because other peptides related to ACE metabolism, such as BK, BK1-5, Ac-SDKP, and Ang 1-7, were inactive.…”

Section: Discussionmentioning

confidence: 98%

Angiotensin II Binding to Angiotensin I–Converting Enzyme Triggers Calcium Signaling

et al. 2011

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 98%

Angiotensin II Binding to Angiotensin I–Converting Enzyme Triggers Calcium Signaling

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Ang II-TOAC, an Ang II analogue containing the TOAC (2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid) spin label synthesized by solid phase methodology [23] and Ang-(1 -7)-FMOC, an Ang-(1 -7) analogue containing the FMOC (9-fluorenylmethyloxycarbonyl) group was used for protection of the amine function [24]. These peptides were supplied by dr. C.R.…”

Section: Peptidesmentioning

confidence: 99%

Effects on Cell Viability and on Apoptosis in Tumoral (MCF-7) and in Normal (MCF10A) Epithelial Breast Cells after Human Chorionic Gonadotropin and Derivated-Angiotensin Peptides Treatments

Noronha¹,

Bernardo²,

Barros³

et al. 2013

JCT

View full text Add to dashboard Cite

Angiotensin-(1 -7) ] is an endogenous heptapeptide hormone of the renin-angiotensin system that has antiproliferative properties. The aim of this work was to evaluate the anti-proliferative and pro-apoptotic properties of Ang-(1 -7) and of Ang-(1 -7)-substituents 9-fluorenylmethyloxycarbonyl (Fmoc) e Ang II-derivatives containing the TOAC (2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid) in normal (MCF10A) and in tumoral (MCF7) epithelial mammary cell lines. Both cell lines received an hCG and angiotensin peptides 24-hour treatment, in combination or alone followed by cell viability, apoptosis and cell cycle assays performed by flow cytometer (GUAVA). After hCG, Ang-(1 -7), hCG + Ang-(1 -7) and hCG + Ang-(1 -7)-Fmoc treatments, MCF7 displayed cell viability decrease and mid-apoptosis increase. We also observed cell viability decrease in MCF10A after Ang-(1 -7), Ang-(1 -7) Fmoc and hCG + AngII Toac treatments. These cells had an increase in late apoptosis and necrosis after AngII Toac, hCG + Ang-(1 -7) and hCG + Ang-(1 -7)-Fmoc treatments. Regarding the cell cycle analysis, we did not observed any changes in cell cycle phases. In summary, cell viability was decreased and apoptosis (initial, mid and late) was increased after hCG and/or Ang-(1 -7) peptides treatments. These results point out hCG and Ang-(1 -7) as effective compounds to inhibit cell proliferation, since they decrease cell viability and increase apoptosis in both normal and in tumoral breast cells, being the effect more pronounced in the tumoral cell line. Our results support the idea of investigating more closely the putative use of these compounds as novel therapeutic agents for breast cancer.

show abstract

“…In the particular case of Toac-bearing peptides, the synthesis procedure used a combined t-Boc and Fmoc strategies as earlier described. 19,20) The analogues produced by gamma irradiation experiments were purified through Waters Delta 600 preparative HPLC (semipreparative octadecyl (C 18 ) column) (Vydac, Hesperia, CA, U.S.A.). In this step, solvents A and B were aqueous 0.02 m ammonium acetate (pH 5) and 60% acetonitrile (ACN) in solvent A, respectively (linear gradient of 30-70% B for 2 h, flow rate of 10 mL/min at 220 nm).…”

Section: Methodsmentioning

confidence: 99%

“…Following with previous studies initiated with AngII and BK, 11,12) these two peptides were now examined under complementary approaches by coupling in their structures, the amino acid-type probe Toac, introduced earlier in the chemistry of peptides. 18,19) Thus, Toac 1 -AngII, Toac 0 -BK and Toac 3 -BK paramagnetically labeled derivatives, earlier evaluated in terms of structure-function relationships, [20][21][22] were tested towards their molecular stability under strong electromagnetic radiation procedure. The reason for this option lied on the fact that as Toac is a stable free radical, it would be affected by the submission approach to strong gamma ray irradiation.…”

mentioning

confidence: 99%

Peptide Structure Modifications: Effect of Radical Species Generated by Controlled Gamma Ray Irradiation Approach

Vieira

Nardi

Nascimento

et al. 2013

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

The present work aimed at evaluating the radiolysis effect upon a set of peptides, most of them involved in physiological functions. To generate reactive radical species, a Co 60 source (up to 15 kGy) was used for controlled gamma irradiation of some peptide solutions including derivatives attaching the stable free radical Toac (2,2,6,6-tetramethypiperidine-1-oxyl-4-amino-4-carboxylic acid). Regardless of the peptide sequence, a nonlinear and progressive degradation of a total of nine peptides was detected. The results were interpreted in the light of the half-life dose (D 1/2 ) parameter which represents the dose necessary for 50% peptide structure degradation. The vasoactive angiotensin II (AngII)'s analogue Ang-(1-7) showed greater stability towards gamma ray radiation than bradykinin (BK), Toac 0 -BK, Pro 4 -BK (D 1/2 around 4 and 2 kGy, respectively) which decreased to about 0.5-1.0 kGy in the case of acetyl-α-melanocyte-stimulating hormone (Ac-α-MSH) and substance P (SP). In terms of peptide structural modifications, the data acquired from different analytical methods suggested a Phe to Tyr (or its ortho and/or meta isomers) transformation as a consequence of the hydroxyl moiety insertion. Noteworthy, this effect seemed to be position-dependent as only Phe located at or near the C-terminal portion seemed to display this transformation. In contrast, Met is comparatively more easily oxidized, thus allowing to conclude that gamma irradiation may induce a complex position and/ or sequence-dependent effect on peptides. As previously applied for BK, some irradiated peptides were submitted to their by-products purification, indeed a complementary target of the present approach for development of uncommon analogues for further structure-function investigation.

show abstract

Synthesis and pharmacological properties of TOAC-labeled angiotensin and bradykinin analogs

Cited by 44 publications

References 28 publications

Angiotensin II Binding to Angiotensin I–Converting Enzyme Triggers Calcium Signaling

Angiotensin II Binding to Angiotensin I–Converting Enzyme Triggers Calcium Signaling

Effects on Cell Viability and on Apoptosis in Tumoral (MCF-7) and in Normal (MCF10A) Epithelial Breast Cells after Human Chorionic Gonadotropin and Derivated-Angiotensin Peptides Treatments

Peptide Structure Modifications: Effect of Radical Species Generated by Controlled Gamma Ray Irradiation Approach

Contact Info

Product

Resources

About