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Nadeem-ul-Haque, Muhammad, Bashir, Anila, Karim, Humira, Khan, Sadiq Noor, Shah, Zafar Ali, Jabeen, Almas, Qayyum, Shaista, Ganesan, A. 
ORCID: https://orcid.org/0000-0003-4862-7999, Choudhary, M. Iqbal and Shaheen, Farzana
(2022)
Synthesis of [1-8-NαC]-zanriorb A1, alanine-containing analogues, and their cytotoxic and anti-inflammatory activity.
Journal of Peptide Science, 28 (8).
ISSN 1075-2617
Abstract
The synthesis of the orbitide[1-8-NαC]-zanriorb A1, isolated from the medicinal plant Zanthoxylum riedelianum, was investigated by solution-phase macrocyclization of a linear peptide and on-resin solid-phase macrocyclization with an acylsulfonamide safety-catch linker. The solution-phase route produced a mixture of proline rotamers, and the main component was assigned as the trans, cis rotamer, identical to the natural product. The on-resin cyclization was less successful, producing mainly a linear peptide, and minor cyclic products as rotameric mixtures. Although the natural product was reported to be significantly cytotoxic against Jurkat leukemia T cells, our synthetic peptides were inactive, suggesting the presence of other rotamers or impurities in the naturally isolated material. Additional analogues of zanriorb A1 were synthesized in which proline and glycine residues were replaced with alanine. While these analogues were not cytotoxic, several of them inhibited the production of nitric oxide in lipopolysaccharide (LPS)-stimulated macrophages. The most active compound, cyclic[Ala5,6,8]-zanriorb A1 had an IC50 of 22 μM and was more potent compared with the standard NG-monomethyl-l-arginine acetate (L-NMMA) with an IC50 of 98 μM, indicating their strong anti-inflammatory potential.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: This work was supported by a grant 5738/Sindh/NRPU/R&D/HEC/2016 from Higher Education Commission Pakistan, and a grant PSF/NSLP/S‐HEJ (290) from the Pakistan Science Foundation. Publisher Copyright: © 2022 European Peptide Society and John Wiley & Sons, Ltd. |
| Uncontrolled Keywords: | anti-inflammatory agents,cyclic peptides,orbitides,orbitide[1-8-nαc]-zanriorb a1,proline rotamers,solid-phase synthesis,structural biology,biochemistry,molecular medicine,molecular biology,pharmacology,drug discovery,organic chemistry ,/dk/atira/pure/subjectarea/asjc/1300/1315 |
| Faculty \ School: | Faculty of Science > School of Chemistry, Pharmacy and Pharmacology |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 11 Jan 2025 01:03 |
| Last Modified: | 18 Jan 2025 01:08 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/98168 |
| DOI: | 10.1002/psc.3405 |
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