2′, 6′-Dimethylphenylalanine : A Useful Aromatic Amino Acid Surrogate for Tyr or Phe Residue in Opioid Peptides
Joint Authors
Source
International Journal of Medicinal Chemistry
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-05-21
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Sasaki, Yusuke& Ambo, Akihiro. 2012. 2′, 6′-Dimethylphenylalanine : A Useful Aromatic Amino Acid Surrogate for Tyr or Phe Residue in Opioid Peptides. International Journal of Medicinal Chemistry،Vol. 2012, no. 2012, pp.1-11.
https://search.emarefa.net/detail/BIM-476536
Modern Language Association (MLA)
Sasaki, Yusuke& Ambo, Akihiro. 2′, 6′-Dimethylphenylalanine : A Useful Aromatic Amino Acid Surrogate for Tyr or Phe Residue in Opioid Peptides. International Journal of Medicinal Chemistry No. 2012 (2012), pp.1-11.
https://search.emarefa.net/detail/BIM-476536
American Medical Association (AMA)
Sasaki, Yusuke& Ambo, Akihiro. 2′, 6′-Dimethylphenylalanine : A Useful Aromatic Amino Acid Surrogate for Tyr or Phe Residue in Opioid Peptides. International Journal of Medicinal Chemistry. 2012. Vol. 2012, no. 2012, pp.1-11.
https://search.emarefa.net/detail/BIM-476536
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-476536