Effects of Amino Acid Chirality and the Chemical Linker on the Cell Permeation Characteristics of Cyclic Prodrugs of Opioid Peptides

2006 ◽  
Vol 49 (4) ◽  
pp. 1261-1270 ◽  
Author(s):  
Bianca M. Liederer ◽  
Tarra Fuchs ◽  
David Vander Velde ◽  
Teruna J. Siahaan ◽  
Ronald T. Borchardt
Keyword(s):  
Amino Acid ◽  
Opioid Peptides ◽  
Cyclic Prodrugs

ChemInform Abstract: Synthesis of Coumarin-Based, Esterase-Sensitive Cyclic Prodrugs of Opioid Peptides with Enhanced Membrane Permeability and Enzymic Stability

ChemInform ◽  
2010 ◽  
Vol 31 (32) ◽  
pp. no-no
Author(s):  
Binghe Wang ◽  
Daxian Shan ◽  
Wei Wang ◽  
Huijuan Zhang ◽  
Olafur Gudmundsson ◽  
...  
Keyword(s):  
Membrane Permeability ◽  
Opioid Peptides ◽  
Cyclic Prodrugs

scholarly journals , -Dimethylphenylalanine : A Useful Aromatic Amino Acid Surrogate for Tyr or Phe Residue in Opioid Peptides

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Yusuke Sasaki ◽  
Akihiro Ambo
Keyword(s):  
Amino Acid ◽  
Opioid Peptides ◽  
Aromatic Amino Acid ◽  
Aromatic Amino Acids ◽  
Hydroxyl Group ◽  
Peptide Mimetics ◽  
Structural Elements ◽  
Receptor Selectivity ◽  
Receptor Affinity ◽  
High Affinity

Two aromatic amino acids, Tyr1 and Phe3 or Phe4, are important structural elements in opioid peptides because they interact with opioid receptors. The usefulness of an artificial amino acid residue ,-dimethylphenylalanine (Dmp) was investigated as an aromatic amino acid surrogate for several opioid peptides, including enkephalin, dermorphin, deltorphin, endomorphin, dynorphin A, and nociceptin peptides. In most peptides, substitutions of Phe3 by a Dmp residue produced analogs with improved receptor-binding affinity and selectivity, while the same substitution of Phe4 induced markedly reduced receptor affinity and selectivity. Interestingly, replacement of Tyr1 by Dmp produced analogs with unexpectedly high affinity or produced only a slight drop in receptor affinity and bioactivity for most peptides. Thus, Dmp is also a useful surrogate for the N-terminal Tyr residue in opioid peptides despite the lack of a phenolic hydroxyl group, which is considered necessary for opioid activity. The Dmp1-substituted analogs are superior to ,-dimethyltyrosine (Dmt)1-substituted analogs for high receptor selectivity since the latter generally have poor receptor selectivity. Thus, Dmp is very useful as an aromatic amino acid surrogate in opioid peptides and may be useful for developing other novel peptide mimetics with high receptor specificity.

Peptides with Morphine-like Action in the Brain

1977 ◽  
Vol 130 (3) ◽  
pp. 298-304 ◽  
Author(s):  
Hans W. Kosterlitz ◽  
John Hughes
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Opioid Peptides ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Methionine Enkephalin ◽  
Therapeutic Implications ◽  
The Brain ◽  
Development Of Tolerance

SummaryThe reasons which led to the search in the brain for substances with morphine-like actions are discussed. Two pentapeptides, methionine-enkephalin and leucine-enkephalin, were isolated. The amino acid sequence of methionine-enkephalin occurs also in the pituitary prohormone β-lipotropin, of which longer fragments (endorphins) of up to 31 amino acids exhibit strong morphine-like action.The physiological significance of these short and long opioid peptides is discussed, particularly with regard to their possible roles as neurotransmitter or neuromodulator.With regard to the mechanisms involved in the development of tolerance to and dependence on opiates, the importance of interaction between the endogenous opioid peptides and the exogenous opiate alkaloids is stressed.The possible therapeutic implications are discussed briefly.

scholarly journals Opiate receptors and opioid peptides: "The poppies of the mind"

1982 ◽  
Vol 1 (4) ◽  
pp. 195-198
Author(s):  
B. J. Meyer
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Sequence ◽  
Opioid Peptides ◽  
Opiate Receptors ◽  
The Mind ◽  
The Brain ◽  
Intensive Search

In 1964 β-lipotropin, a compound consisting of 91 amino acids, was isolated from the adenohypophysis. In 1973, opiate receptors were found to be present in different areas of the brain and it was postulated that the brain probably produces opiate-like substances which react with these receptors. This finding was followed with an intensive search for opiate-like substances, resulting in the isolation of two groups of substances which react with the opiate receptors. These were named the encephalins and the endorphins. All members of these two groups were either peptides or polypeptides and the amino-acid sequence of each corresponded to the amino-acid sequence of specific segments of β-lipotropin.

Antinociceptive Effects of VV-Hemorphin-5 Peptide Analogues Containing Aminophosphonate Moiety in Mouse Formalin Model of Pain

2020 ◽  
Vol 27 ◽  
Author(s):  
Borislav Assenov ◽  
Daniela Pechlivanova ◽  
Elena Dzhambazova ◽  
Petia Peneva ◽  
Petar Todorov
Keyword(s):  
Amino Acid ◽  
Opioid Peptides ◽  
Inflammatory Pain ◽  
Solid Phase ◽  
Antinociceptive Effect ◽  
Solid Phase Peptide Synthesis ◽  
Experimental Pain ◽  
Formalin Injection ◽  
Endogenous Opioid ◽  
Peptide Analogues

Background: Hemorphins are endogenous hemoglobin-derived peptides that belong to the family of “atypical” opioid peptides with both affinities to opioid receptors and ability to release other endogenous opioid peptides. Objective: In the present study, peptide analogues of Valorphin (VV-hemorphin-5) containing amino phosphonate moiety synthesized by solid-phase peptide synthesis (Fmoc-strategy) were investigated for their potential antinociceptive activities and compared to the reference VV-H in formalin-induced model of acute and inflammatory pain in mice. Methods: The hemorphin analogues were prepared by replacement of the one and/or two N-terminal Val in VV-hemorphin5 (VV-H) with ((dimethoxy phosphoryl) methyl)-L-valine and ((dimethoxy phosphoryl) methyl)-L-leucine to obtained the compounds pVV-H, pL-H, and pLV-H. Aiming to additionally prove the importance of amino acid valine, we introduced the ((dimethoxy phosphoryl) methyl)-L-leucine to the N-side of VV-hemorphin-5 (pLVV-H). The experiments were carried out on adult male ICR mice. All peptides were administered intracerebroventricularly at three doses (50, 25 and 12,5 µg/mouse). We have studied the effects of the peptides on acute (1st phase) and inflammatory (2nd phase) pain reaction using un experimental model with intraplantar formalin injection. Results: VV-H showed a significant antinociceptive effect both in the acute and inflammatory phases of the test. Although Valorphin hexa-, hepta-, and octapeptide analogs demonstrated a significant antinociceptive effect, they showed substantial differences considering their effective dose and the phase of the test as compared to the Valorphin. Discussion: Data showed that modified heptapeptides pVV-H and pLV-H exerted the same or better antinociception in acute and inflammatory pain, in comparison to the reference peptide, while pL-H and pLVV-H analogues were less effective. Conclusion: Our study contributes to the elucidation of the role of Valine and the number of amino acid residues in the structure of hemorphin peptide analogs in their effectiveness in suppressing both acute and inflammatory experimental pain.

The effect of conformation of the acyloxyalkoxy‐based cyclic prodrugs of opioid peptides on their membrane permeability

1999 ◽  
Vol 53 (4) ◽  
pp. 403-413 ◽  
Author(s):  
O.S. Gudmundsson ◽  
D.G. Vander Velde ◽  
S.D.S. Jois ◽  
A. Bak ◽  
T.J. Siahaan ◽  
...  
Keyword(s):  
Membrane Permeability ◽  
Opioid Peptides ◽  
Cyclic Prodrugs

Significant differences in the disposition of cyclic prodrugs of opioid peptides in rats and guinea pigs following IV administration

2005 ◽  
Vol 94 (12) ◽  
pp. 2676-2687 ◽  
Author(s):  
Bianca M. Liederer ◽  
Kimthoa t. Phan ◽  
Hui ouyang ◽  
Ronald T. Borchardt
Keyword(s):  
Opioid Peptides ◽  
Guinea Pigs ◽  
Cyclic Prodrugs
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