Biological activity of the novel cyclic angiotensin II analogue [Sar1,Lys3,Glu5]ANG II

Vlahakos, Demetrios; Matsoukas, John; Ancans, Juris; Moore, Graham J.; Iliodromitis, Efstathios K.; Marathias, Katerina; Kremastinos, Dimitrios Th.

doi:10.1007/bf00128106

Cited by 11 publications

(17 citation statements)

References 5 publications

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“…Furthermore, the ring cluster conformation is supported by the design and synthesis of novel constrained AII cyclic analogues [Sar1,Lys3,Glu5]AII, [Sar1,Asp3,Glu5]AII, which possess agonist activities when tested in the rat uterus assay and in anesthetized rabbits [56,57]. These potent cyclic analogues were designed to have a major molecular feature, the integrity of the ring cluster [58][59][60]. This model has enabled us to further explore spatial characteristics of AII pharmacophore groups and to design and synthesize nonpeptide losartan analogues.…”

Section: Discussionmentioning

confidence: 99%

An efficient synthesis of a rationally designed 1,5 disubstituted imidazole AT1 Angiotensin II receptor antagonist: reorientation of imidazole pharmacophore groups in losartan reserves high receptor affinity and confirms docking studies

Agelis

Roumelioti

Resvani

et al. 2010

J Comput Aided Mol Des

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A new 1,5 disubstituted imidazole AT(1) Angiotensin II (AII) receptor antagonist related to losartan with reversion of butyl and hydroxymethyl groups at the 2-, 5-positions of the imidazole ring was synthesized and evaluated for its antagonist activity (V8). In vitro results indicated that the reorientation of butyl and hydroxymethyl groups on the imidazole template of losartan retained high binding affinity to the AT(1) receptor concluding that the spacing of the substituents at the 2,5- positions is of primary importance. The docking studies are confirmed by binding assay results which clearly show a comparable binding score of the designed compound V8 with that of the prototype losartan. An efficient, regioselective and cost effective synthesis renders the new compound as an attractive candidate for advanced toxicological evaluation and a drug against hypertension.

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Section: Discussionmentioning

confidence: 99%

An efficient synthesis of a rationally designed 1,5 disubstituted imidazole AT1 Angiotensin II receptor antagonist: reorientation of imidazole pharmacophore groups in losartan reserves high receptor affinity and confirms docking studies

Agelis

Roumelioti

Resvani

et al. 2010

J Comput Aided Mol Des

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“…[ [87][88][89][90][91][92][93][94][95][96][97][98][99] analogue, could indicate that the mechanism of inhibition is not due to binding competition, but rather due to the delivery of a negative signal by the antagonist, which overcomes the agonist response possibly through the activation of antigen specific regulatory T cells, or induction of immunosuppressive cytokines such as IL-10 by T cells. Lower activity of cyclo (91)(92)(93)(94)(95)(96)(97)(98)(99) [20,101,102].…”

Section: Cyclic Analogues As Immunogensmentioning

confidence: 99%

“…The linear MBP [87][88][89][90][91][92][93][94][95][96][97][98][99] and cyclo (87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(99) [20]. The linear MBP [87][88][89][90][91][92][93][94][95][96][97][98][99] and cyclo (87)(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(99) …”

Section: In Vitro Assays With Mbp 87-99 Analoguesmentioning

confidence: 99%

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Round and Round we Go: Cyclic Peptides in Disease

Katsara

Tselios

Deraos³

et al. 2006

CMC

152

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There is a need for novel drugs for the treatment of infectious diseases, autoimmunity and cancer. Cyclic peptides constitute a class of compounds that have made crucial contributions to the treatment of certain diseases. Penicillin, Vancomycin, Cyclosporin, the Echinocandins and Bleomycin are well-known cyclic peptides. Cyclic peptides, compared to linear peptides, have been considered to have greater potential as therapeutic agents due to their increased chemical and enzymatic stability, receptor selectively, and improved pharmacodynamic properties. They have been used as synthetic immunogens, transmembrane ion channels, antigens for Herpes Simplex Virus, potential immunotherapeutic vaccines for diabetes and Experimental Autoimmune Encephalomyelitis - an animal model of Multiple Sclerosis, as inhibitors against alpha-amylase and as protein stabilizers. Herein, we review important cyclic peptides as therapeutic agents in disease.

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“…In an attempt to characterize the bioactive conformation of this hormone, several cyclic analogues have been created by the incorporation of disulfide or lactam bridges and tested for their activity [23][24][25]. Among them, the following bridged monocyclic disulfides demonstrated high affinity for the AT1 receptor: c[Cys 3,5 ]-AII, c[Cys 3 , Hcy 5 ]-AII, c [Hcy 3 , Cys 5 ]-AII and c[Hcy 3,5 ]-AII [23,[26][27][28][29][30][31]. In addition, cyclic analogues were created by inserting a lactam bridge in the same region of the molecule, which generated relevant antagonistic activity [27].…”

Section: Introductionmentioning

confidence: 99%

Biological and conformational evaluation of angiotensin II lactam bridge containing analogues

Oliveira

Fázio

Silva

et al. 2011

Regulatory Peptides

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Angiotensin II (AII) is the active octapeptide product of the renin enzymatic cascade, which is responsible for sustaining blood pressure. In an attempt to establish the AII-receptor-bound conformation of this octapeptide, we designed conformationally constrained analogues by scanning the entire AII sequence with an i-(i+2) and i-(i+3) lactam bridge consisting of an Asp-(Xaa)(n)-Lys scaffold. Most analogues presented low agonistic activity when compared to AII in the different bioassays tested. The exceptions are cyclo(0-1a) [Asp(0), endo-(Lys(1a))]-AII (1) and [Asp(0), endo-(Lys(1a))]-AII (2), both of which showed activity similar to AII. Based on peptide 1 and the analogue cyclo(3-5)[Sar(1), Asp(3), Lys(5)]-AII characterized by Matsoukas et al., we analyzed the agonistic and antagonistic activities, respectively, through a new monocyclic peptide series synthesized by using the following combinations of residues as bridgehead elements for the lactam bond formation: D- or L-Asp combined with D- or L-Lys or L-Glu combined with L-Orn. Six analogues showed an approximately 20% increase in biological activity when compared with peptide (1) and were equipotent to AII. In contrast, six analogues presented antagonistic activity. These results suggest that the position of the lactam bridge is more important than the bridge length or chirality for recognition of and binding to the angiotensin II AT1-receptor.

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Biological activity of the novel cyclic angiotensin II analogue [Sar1,Lys3,Glu5]ANG II

Cited by 11 publications

References 5 publications

An efficient synthesis of a rationally designed 1,5 disubstituted imidazole AT1 Angiotensin II receptor antagonist: reorientation of imidazole pharmacophore groups in losartan reserves high receptor affinity and confirms docking studies

An efficient synthesis of a rationally designed 1,5 disubstituted imidazole AT1 Angiotensin II receptor antagonist: reorientation of imidazole pharmacophore groups in losartan reserves high receptor affinity and confirms docking studies

Round and Round we Go: Cyclic Peptides in Disease

Biological and conformational evaluation of angiotensin II lactam bridge containing analogues

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