Synthesis and biological activity of branched enkephalin analogues containing two amino acids in a side chain

Bobrova, I. V.; Mishlakova, Natalia; Selander, Anette; Mekshun, Elena; Rozental, G.

doi:10.1016/s0223-5234(98)80066-4

Cited by 3 publications

(2 citation statements)

References 4 publications

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“…As a part of our effort to obtain new enkephalin analogues [3][4][5] we have synthesized several new compounds with a cardioprotective profile [6] and tested them in a rat model of infarction.…”

Section: Introductionmentioning

confidence: 99%

Eribis Peptide 94 Mimics Ischemic Preconditioning in Rats with an Acute Myocardial Infarction and has Cardioprotective Effects during Prolonged Ischemia

2014

J Pharm Pharmacol

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Objectives: Previously, we demonstrated that a novel enkephalin analogue, Eribis Peptide 94 (EP94), produces a reduction of myocardial infarct size in rats and pigs administrated during occlusion. Since a complete dose-response relationship and the opioid receptor subtype activated by EP94 was not been clearly established, the following study was undertaken. It was also determined if multiple doses of EP94 could produce greater cardioprotective effects similar to those observed with single versus multiple ischemic preconditioning (IPC) stimuli. Methods: We used adult male Sprague-Dawley rats subjected to either 25 or 40 minutes of coronary occlusion followed by 120 minutes of reperfusion. Key findings: A single and triple bolus of 1 µg/kg of EP94 administered iv prior occlusion produced a reduction of infarct size (IS/ AAR) by 39% and 45%, correspondingly. Dose-response relationship has been established. All of the opioid receptor antagonists (naloxone, CTOP, naltrindole, nor-BNI) blocked the effect of EP94. Conclusion: EP94 produces a potent cardioprotective effect in rats following single or multiple injections administrated prior occlusion via effects on µ, δ, and κ opioid receptors. Repeated bolus injections of EP94 produced a reduction of IS/AAR when the ischemic period was increased from 25 to 40 minutes.

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Section: Introductionmentioning

confidence: 99%

Eribis Peptide 94 Mimics Ischemic Preconditioning in Rats with an Acute Myocardial Infarction and has Cardioprotective Effects during Prolonged Ischemia

2014

J Pharm Pharmacol

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“…Lysine contains two amino groups and thus may give rise to isopeptides (ε‐peptides) by forming N ε amide bonds, in addition to the usual peptides containing N α bonds. The occurrence of lysine N ε bonds and related branched structures is well documented and lysine‐based cross‐links are often of fundamental importance in key biochemical processes such as the ubiquitin‐proteasome pathway (16–22). When the sector of chemotactic agents is examined, it can be seen that the Lys residues, engaged through the usual N α bonds, are found in several formylated and nonformylated models which are often endowed with bioactivity and selectivity of action (8,23–25).…”

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confidence: 99%

Isopeptide bonds in chemotactic tripeptides. Synthesis and activity of lysine‐containing fMLF analogs

Zecchini¹,

Nalli²,

Mollica³

et al. 2002

The Journal of Peptide Research

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In order to explore the properties of chemotactic N-formylpeptides containing isopeptide bonds within their backbones, a group of lysine-containing analogs of the prototypical chemotactic tripeptide N-formylmethionyl-leucyl-phenylalanine (fMLF) was synthesized. The new analogs were designed by adding to the HCO-Met or Boc-Met residue a dipeptide fragment made up of Lys and Phe residues joined through Lys N alpha or N epsilon bonds, in all possible combinations. Thus, the following six pairs of tripeptides were synthesized and examined for their bioactivity: RCO-Met-Lys(Z)-Phe-OMe (2a, b), RCO-Met-Lys(Z-Phe)-OMe (3a, b), Z-Lys(RCO-Met)-Phe-OMe (4a, b), Z-Phe-Lys(RCO-Met)-OMe (5a, b), RCO-Met-Phe-Lys(Z)-OMe (6a, b) and Z-Lys(RCO-Met-Phe)-OMe (7a, b), with R=OC(CH3)(3 )and R=H for compounds a and b, respectively. All the new models were characterized fully and their activity (chemotaxis, superoxide anion production and lysozyme release) on human neutrophils determined as agonists (compounds b) and antagonists (compounds a). All N-formyl derivatives 2b-7b are less potent than fMLF-OMe as chemoattractants, but compound 7b exhibits selective activity as superoxide anion producer. Derivatives 2a-7a do not show antagonistic activity towards fMLF induced chemotaxis and O(2)(-) production, however, all these compounds except 4a antagonize lysozyme release by 60%.

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ChemInform Abstract: Synthesis and Biological Activity of Branched Enkephalin Analogues Containing Two Amino Acids in a Side Chain

et al. 1998

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Synthesis and biological activity of branched enkephalin analogues containing two amino acids in a side chain

Cited by 3 publications

References 4 publications

Eribis Peptide 94 Mimics Ischemic Preconditioning in Rats with an Acute Myocardial Infarction and has Cardioprotective Effects during Prolonged Ischemia

Eribis Peptide 94 Mimics Ischemic Preconditioning in Rats with an Acute Myocardial Infarction and has Cardioprotective Effects during Prolonged Ischemia

Isopeptide bonds in chemotactic tripeptides. Synthesis and activity of lysine‐containing fMLF analogs

ChemInform Abstract: Synthesis and Biological Activity of Branched Enkephalin Analogues Containing Two Amino Acids in a Side Chain

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