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

被引：5

作者：

Baumann, Markus ^{[1
,2
]}

Hussain, Mohammad Musarraf ^{[1
,2
,5
]}

Henne, Nina ^{[1
,2
]}

Garrote, Daniel Moya ^{[1
,2
]}

Karlshoj, Stefanie ^{[3
]}

Fossen, Torgils ^{[1
,2
]}

Rosenkilde, Mette M. ^{[3
]}

Vabeno, Jon ^{[4
]}

Haug, Bengt Erik ^{[1
,2
]}

机构：

[1] Univ Bergen, Dept Chem, Allegaten 41, NO-5007 Bergen, Norway

[2] Univ Bergen, Ctr Pharm, Allegaten 41, NO-5007 Bergen, Norway

[3] Univ Copenhagen, Fac Hlth & Med Sci, Dept Neurosci & Pharmacol, Mol Pharmacol Lab, Blegdamsvej 3, DK-2200 Copenhagen, Denmark

[4] UiT Arctic Univ Norway, Dept Pharm, Fac Hlth Sci, NO-9037 Tromso, Norway

[5] Jagannath Univ, Dept Pharm, Dhaka 1100, Bangladesh

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2017年 / 25卷 / 02期

基金：

英国医学研究理事会;

关键词：

CXCR4; antagonist; Peptidomimetic; Scaffold; SOLID-PHASE SYNTHESIS; PEPTIDE-HETEROCYCLE HYBRIDS; CELL FUSION; INHIBITOR; SDF-1; COMBINATION; LESTR/FUSIN; TACHYPLESIN; HEMOCYTES; DESIGN;

D O I：

10.1016/j.bmc.2016.11.036

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Here we report a series of close analogues of our recently published scaffold-based tripeptidomimetic CXCR4 antagonists, containing positively charged guanidino groups in R-1 and R-2, and an aromatic group in R-3. While contraction/elongation of the guanidine carrying side chains (R-1 and R-2) resulted in loss of activity, introduction of bromine in position 1 on the naphth-2-ylmethyl moiety (R-3) resulted in an EC50 of 61 mu M (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. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：646 / 657

页数：12

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