What peptides these deltorphins be1Paraphrased from Lucius Annaeus Seneca, “What fools these mortals be,” ca 4BCE–65ACE; Epistles 1, 3.1

Lazarus, Lawrence H.; Bryant, Sharon D.; Cooper, P. S.; Salvadori, Severo

doi:10.1016/s0301-0082(98)00050-1

Cited by 71 publications

(5 citation statements)

References 337 publications

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“…In addition, the Dmt 1 -substituted YRFB exhibited great affinity for both the μ - and δ -receptors, which often resulted in low receptor selectivity. Such trends have also been observed with other Dmt 1 -substituted opioid peptides [ 39 , 64 , 65 ]. In contrast, substitution of Dmp 1 for Tyr 1 improved μ -receptor selectivity exclusively, a result distinct from the effects of Dmt 1 substitution.…”

Section: Dmp Replacement Of N-terminal Tyr Residue In Opioid Peptisupporting

confidence: 74%

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

Sasaki

Ambo

2012

International Journal of Medicinal Chemistry

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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 2′,6′-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 2′,6′-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.

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Section: Dmp Replacement Of N-terminal Tyr Residue In Opioid Peptisupporting

confidence: 74%

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

Sasaki

Ambo

2012

International Journal of Medicinal Chemistry

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“…We earlier tested several peptides derived of dermorphins and deltorphins (Amiche et al 1998; Lazarus et al 1999; Negri et al 2000). These were, however, unstable and apparently degraded by traces of proteases present in the enzyme preparation (Jilek et al 2005).…”

Section: Resultsmentioning

confidence: 99%

Substrate specificity of a peptidyl-aminoacyl-l/d-isomerase from frog skin

et al. 2011

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In the skin of fire-bellied toads (Bombina species), an aminoacyl-l/d-isomerase activity is present which catalyses the post-translational isomerization of the l- to the d-form of the second residue of its substrate peptides. Previously, this new type of enzyme was studied in some detail and genes potentially coding for similar polypeptides were found to exist in several vertebrate species including man. Here, we present our studies to the substrate specificity of this isomerase using fluorescence-labeled variants of the natural substrate bombinin H with different amino acids at positions 1, 2 or 3. Surprisingly, this enzyme has a rather low selectivity for residues at position 2 where the change of chirality at the alpha-carbon takes place. In contrast, a hydrophobic amino acid at position 1 and a small one at position 3 of the substrate are essential. Interestingly, some peptides containing a Phe at position 3 also were substrates. Furthermore, we investigated the role of the amino-terminus for substrate recognition. In view of the rather broad specificity of the frog isomerase, we made a databank search for potential substrates of such an enzyme. Indeed, numerous peptides of amphibia and mammals were found which fulfill the requirements determined in this study. Expression of isomerases with similar characteristics in other species can therefore be expected to catalyze the formation of peptides containing d-amino acids.Electronic supplementary materialThe online version of this article (doi:10.1007/s00726-011-0890-6) contains supplementary material, which is available to authorized users.

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“…These peptides are good examples of the importance of stereochemistry in biology. They are both part of the frog's defense mechanism and highly selective ligands to μ- and δ-opioid receptors, respectively. The activity of these peptides is inherent to d -Ala 2 forms, while all- l forms are found to be biologically inactive.…”

Section: Resultsmentioning

confidence: 99%

Distinguishing and Quantifying Peptides and Proteins Containingd-Amino Acids by Tandem Mass Spectrometry

Adams

Zubarev

2005

Anal. Chem.

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Tandem mass spectrometry (MS/MS) utilizing both electron capture dissociation (ECD) and collisionally activated dissociation (CAD) was used to develop a qualitative and quantitative analytical method for chiral analysis of individual amino acid residues in polypeptides. ECD produced a more distinct chiral recognition than CAD, which is attributed to the smaller degree of vibrational excitation in ECD. Several peptide and protein model systems were used in this study, including the smallest known protein, tryptophan cage, a lactoferrin peptide, and the biologically relevant opioid peptide, dermorphin. An adaptation of the kinetic method was used to quantify the degree of separation between fragmentation patterns of stereoisomeric peptides as a function of fragment ion abundances. The obtained calibration scale for relative abundances of d-amino acids in diastereomeric peptide mixtures was accurate to 1% for ECD and to 3-5% for CAD. It was found that separation and quantification of stereoisomers could be advantageously performed by nanoflow reversed-phase liquid chromatography, with the objective of on-line MS/MS limited to stereoisomer identification. This technique shows promise for the analysis of chiral substitution in peptides and proteins, broadening the application area for tandem mass spectrometry.

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What peptides these deltorphins be1Paraphrased from Lucius Annaeus Seneca, “What fools these mortals be,” ca 4BCE–65ACE; Epistles 1, 3.1

Cited by 71 publications

References 337 publications

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

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

Substrate specificity of a peptidyl-aminoacyl-l/d-isomerase from frog skin

Distinguishing and Quantifying Peptides and Proteins Containingd-Amino Acids by Tandem Mass Spectrometry

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