Biological and conformational evaluation of angiotensin II lactam bridge containing analogues

Oliveira, Vani Xavier; Fázio, Marcos A.; Silva, Adriana F.; Campana, Patricia T.; Pesquero, João Bosco; Santos, Edson Lucas dos; Costa-Neto, Cláudio M.; Miranda, Antônio

doi:10.1016/j.regpep.2011.05.015

Cited by 13 publications

(13 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Peptides were cleaved and deprotected in anhydrous hydrogen fluoride (HF) and purified by RP-HPLC. Analysis by RP-HPLC and capillary electrophoresis (CE) revealed that the purity of all synthesized compounds exceeded 96% [32]. Peptides were characterized by an amino acid analysis and LC/ESI(+)-MS. Figure 1 shows the anti-plasmodium activity of the AII analogs as quantitated by the fluorescence microscopy.…”

Section: Membrane Permeability Assaymentioning

confidence: 99%

“…This fundamental limitation of AII highlights the necessity for the derivation and synthesis of new compounds based on its structure that maintain its anti‐malarial effects while eliminating its biological effects on humans. Several AII analogs were synthesized with two modified N ‐terminal amino acid residues (Asp and Lys), resulting in the intramolecular formation of lactam bridges and the induction of a structural folding that increases the ability of these antimicrobial peptides to disrupt the lipid membranes of plasmodia . To determine how these lactam bridges enhance anti‐malarial activity, we synthesized the corresponding linear peptides – without lactam bridges.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A study of the anti‐plasmodium activity of angiotensin II analogs

Chamlian

Bastos

Maciel

et al. 2013

Journal of Peptide Science

Self Cite

View full text Add to dashboard Cite

Controlling the dissemination of malaria requires the development of new drugs against its etiological agent, a protozoan of the Plasmodium genus. Angiotensin II and its analog peptides exhibit activity against the development of immature and mature sporozoites of Plasmodium gallinaceum. In this study, we report the synthesis and characterization of angiotensin II linear and cyclic analogs with anti-plasmodium activity. The peptides were synthesized by a conventional solid-phase method on Merrifield's resin using the t-Boc strategy, purified by RP-HPLC and characterized by liquid chromatography/ESI (+) MS (LC-ESI(+)/MS), amino acid analysis, and capillary electrophoresis. Anti-plasmodium activity was measured in vitro by fluorescence microscopy using propidium iodine uptake as an indicator of cellular damage. The activities of the linear and cyclic peptides are not significantly different (p < 0.05). Kinetics studies indicate that the effects of these peptides on plasmodium viability overtime exhibit a sigmoidal profile and that the system stabilizes after a period of 1 h for all peptides examined. The results were rationalized by partial least-square analysis, assessing the position-wise contribution of each amino acid. The highest contribution of polar amino acids and a Lys residue proximal to the C-terminus, as well as that of hydrophobic amino acids in the N-terminus, suggests that the mechanism underlying the anti-malarial activity of these peptides is attributed to its amphiphilic character.

show abstract

Section: Membrane Permeability Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A study of the anti‐plasmodium activity of angiotensin II analogs

Chamlian

Bastos

Maciel

et al. 2013

Journal of Peptide Science

Self Cite

View full text Add to dashboard Cite

show abstract

“…The cyclic analogs were able to inhibit approximately 75% of the sporozoites population, and the linear analogs promoted a decrease between 67% and 87%. Importantly, these analogs did not exhibit effects on blood pressure .…”

Section: Introductionmentioning

confidence: 97%

Antiplasmodial activity study of angiotensin II via Ala scan analogs

Silva

Bastos

Torres

et al. 2014

Journal of Peptide Science

Self Cite

View full text Add to dashboard Cite

Angiotensin II (AII) as well as analog peptides shows antimalarial activity against Plasmodium gallinaceum and Plasmodium falciparum, but the exact mechanism of action is still unknown. This work presents the solid-phase synthesis and characterization of eight peptides corresponding to the alanine scanning series of AII plus the amide-capped derivative and the evaluation of the antiplasmodial activity of these peptides against mature P. gallinaceum sporozoites. The Ala screening data indicates that the replacement of either the Ile(5) or the His(6) residues causes minor effects on the in vitro antiplasmodial activity compared with AII, i.e. AII (88%), [Ala(6) ]-AII (79%), and [Ala(5) ]-AII (75%). Analogs [Ala(3) ]-AII, [Ala(1) ]-AII, and AII-NH2 showed antiplasmodial activity around 65%, whereas the activity of the [Ala(8) ]-AII, [Ala(7) ]-AII, [Ala(4) ]-AII, and [Ala(2) ]-AII analogs is lower than 45%. Circular dichroism data suggest that AII and the most active analogs adopt a β-fold conformation in different solutions. All AII analogs, except [Ala(4) ]-AII and [Ala(8) ]-AII, show contractile responses and interact with the AT1 receptor, [Ala(5) ]-AII and [Ala(6) ]-AII. In conclusion, this approach is helpful to understand the contribution of each amino acid residue to the bioactivity of AII, opening new perspectives toward the design of new sporozoiticidal compounds.

show abstract

“…In an attempt to reduce the degree of conformation freedom, 21,22 we designed conformationally constrained analogues by scanning the residues 3, 6, 7, and 10 important for the biological activity of I-4 while the other residues were left unchanged with the i − (i + 2) lactam bridge consisting of a Glu-Xaa-Lys scaffold.…”

Section: Oral Glucose Tolerance Tests (Ogtts) Of Ii-1-4 Evaluated In mentioning

confidence: 99%

Design, synthesis and biological evaluation of novel peptide MC2 analogues from Momordica charantia as potential anti-diabetic agents

Yang

Zhang

et al. 2015

Org. Biomol. Chem.

View full text Add to dashboard Cite

Three series of Momordica charantia (MC)2 analogues were designed, synthesized and evaluated for their anti-hyperglycaemic effects. Alanine scanning focusing on the peptide MC2 indicated the importance of the residues proline (Pro)(3), serine (Ser)(6), isoleucine (Ile)(7) and Ser(10) for anti-hyperglycaemic effects. Among the first series of MC2 analogues, peptide I-4 exhibited a better anti-hyperglycaemic effect and was chosen for further modification. A further two series of conformationally constrained analogues were designed by scanning the residues Pro(3), Ser(6), Ile(7), and Ser(10) with an i - (i + 2) lactam bridge consisting of a glutamic acid-Xaa-lysine (Glu-Xaa-Lys) scaffold and a diproline fragment. By screening in normal mice and mice with diabetes mellitus, peptides II-1, II-2 and III-3 showed a significant improvement in anti-hyperglycaemic and anti-oxidative activities compared with I-4. These data suggest that II-1, II-2 and III-3 could be candidates for future treatment of diabetes mellitus.

show abstract

Biological and conformational evaluation of angiotensin II lactam bridge containing analogues

Cited by 13 publications

References 47 publications

A study of the anti‐plasmodium activity of angiotensin II analogs

A study of the anti‐plasmodium activity of angiotensin II analogs

Antiplasmodial activity study of angiotensin II via Ala scan analogs

Design, synthesis and biological evaluation of novel peptide MC2 analogues from Momordica charantia as potential anti-diabetic agents

Contact Info

Product

Resources

About