Influence of chain length on the activity of tripeptidomimetic antagonists for CXC chemokine receptor 4 (CXCR4)

Markus Baumann, Mohammad Musarraf Hussain, Nina Henne, Daniel Moya Garrote, Stefanie Karlshoj, Torgils Fossen, Mette M. Rosenkilde, Jon Vabeno, Bengt Erik Haug

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6 Citations (Scopus)

Abstract

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.
Original languageEnglish
JournalBioorganic & Medicinal Chemistry
Volume25
Issue number2
Pages (from-to)646-657
ISSN0968-0896
DOIs
Publication statusPublished - 15 Jan 2017

Keywords

  • CXCR4 antagonist
  • Peptidomimetic
  • Scaffold

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