التفاصيل البيبلوغرافية
| العنوان: |
Conformational Constraint between Aromatic Residue Side Chains in the “Message” Sequence of the Peptide Arodyn Using Ring Closing Metathesis Results in a Potent and Selective Kappa Opioid Receptor Antagonist |
| المؤلفون: |
Solomon A. Gisemba (8292918), Michael J. Ferracane (3114030), Thomas F. Murray (776850), Jane V. Aldrich (2332483) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biophysics, Biochemistry, Cell Biology, Neuroscience, Physiology, Pharmacology, Biotechnology, Evolutionary Biology, Immunology, Cancer, Computational Biology, Chemical Sciences not elsewhere classified, Selective Kappa Opioid Receptor Ant., KOR affinity, 15 nM, Arg 4, analog arodyn, KOR antagonist potency, KOR antagonism, Ring Closing Metathesis Results, Peptide Arodyn, allyl groups, Aromatic Residue Side Chains, para O, K B, drug addiction, Conformational Constraint, docking study, mood disorders, KOR selectivity |
| الوصف: |
Kappa opioid receptor (KOR) antagonists have recently shown potential for treating drug addiction and mood disorders. The linear acetylated dynorphin A analog arodyn (Ac[Phe 1,2,3 ,Arg 4 ,d-Ala 8 ]dynorphin A-(1–11)NH 2 ), synthesized in our laboratory, demonstrated potent and selective KOR antagonism. Cyclization of arodyn could potentially stabilize the bioactive conformation and enhance its metabolic stability. The cyclization strategy employed involved ring closing metathesis between adjacent meta - or para -substituted Tyr(allyl) residues in the “message” sequence that were predicted in a docking study to yield analogs that would bind to the KOR with binding poses similar to arodyn. Consistent with the modeling, the resulting analogs retained KOR affinity similar to arodyn; the peptides involving cyclization between para O -allyl groups also retained high KOR selectivity, with one analog exhibiting KOR antagonist potency ( K B = 15 nM) similar to arodyn. These promising cyclized analogs with constrained aromatic residues represent novel leads for further exploration of KOR pharmacology. |
| نوع الوثيقة: |
dataset |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/dataset/Conformational_Constraint_between_Aromatic_Residue_Side_Chains_in_the_Message_Sequence_of_the_Peptide_Arodyn_Using_Ring_Closing_Metathesis_Results_in_a_Potent_and_Selective_Kappa_Opioid_Receptor_Antagonist/14192745 |
| DOI: |
10.1021/acs.jmedchem.0c01984.s008 |
| الاتاحة: |
https://doi.org/10.1021/acs.jmedchem.0c01984.s008 |
| Rights: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.2553F804 |
| قاعدة البيانات: |
BASE |