Influence of chain length on the activity of tripeptidomimetic antagonists for CXC chemokine receptor 4 (CXCR4)
| Autor: | Mohammad Musarraf Hussain, Torgils Fossen, Markus Baumann, Nina Henne, Daniel Moya Garrote, Bengt Erik Haug, Mette M. Rosenkilde, Jon Våbenø, Stefanie Karlshøj |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Receptors CXCR4 Peptidomimetic CXCR4 antagonist Clinical Biochemistry Pharmaceutical Science Pharmacy Norwegian 01 natural sciences Biochemistry Scaffold Danish 03 medical and health sciences Bridged Bicyclo Compounds Structure-Activity Relationship Drug Discovery medicine Humans CXC chemokine receptors Molecular Biology VDP::Mathematics and natural science: 400::Chemistry: 440 Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry business.industry Organic Chemistry language.human_language 0104 chemical sciences The arctic Chain length 030104 developmental biology VDP::Matematikk og Naturvitenskap: 400::Kjemi: 440 Research council Family medicine language Molecular Medicine Peptidomimetics business |
| Zdroj: | Bioorganic & Medicinal Chemistry |
| ISSN: | 1464-3391 |
| Popis: | Submitted manuscript version. Published version available in Bioorganic and Medicinal Chemistry (2017) 25(2), 646-657. Here we report a series of close analogues of our recently published scaffold-based tripeptidomimetic CXCR4 antagonists, containing positively charged guanidino groups in R1 and R2, and an aromatic group in R3. While contraction/elongation of the guanidine carrying side chains (R1 and R2) resulted in loss of activity, introduction of bromine in position 1 on the naphth-2-ylmethyl moiety (R3 ) resulted in an EC50 of 61 µM (mixture of diastereoisomers) against wild-type CXCR4; thus, the antagonistic activity of these tripeptidomimetics seems to be amenable to optimization of the aromatic moiety. Moreover, for analogues carrying a naphth-2-ylmethyl substituent, we observed that a Pictet-Spengler like cyclization side reaction depended on the nature of the R1 substituent. |
| Databáze: | OpenAIRE |
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