Influence of chain length on the activity of tripeptidomimetic antagonists for CXC chemokine receptor 4 (CXCR4)
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Influence of chain length on the activity of tripeptidomimetic antagonists for CXC chemokine receptor 4 (CXCR4). / Baumann, Markus; Hussain, Mohammad Musarraf; Henne, Nina; Garrote, Daniel Moya; Karlshoj, Stefanie; Fossen, Torgils; Rosenkilde, Mette M.; Vabeno, Jon; Haug, Bengt Erik.
In: Bioorganic & Medicinal Chemistry, Vol. 25, No. 2, 15.01.2017, p. 646-657.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Influence of chain length on the activity of tripeptidomimetic antagonists for CXC chemokine receptor 4 (CXCR4)
AU - Baumann, Markus
AU - Hussain, Mohammad Musarraf
AU - Henne, Nina
AU - Garrote, Daniel Moya
AU - Karlshoj, Stefanie
AU - Fossen, Torgils
AU - Rosenkilde, Mette M.
AU - Vabeno, Jon
AU - Haug, Bengt Erik
PY - 2017/1/15
Y1 - 2017/1/15
N2 - 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.
AB - 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.
KW - CXCR4 antagonist
KW - Peptidomimetic
KW - Scaffold
U2 - 10.1016/j.bmc.2016.11.036
DO - 10.1016/j.bmc.2016.11.036
M3 - Journal article
C2 - 27939345
VL - 25
SP - 646
EP - 657
JO - Bioorganic & Medicinal Chemistry
JF - Bioorganic & Medicinal Chemistry
SN - 0968-0896
IS - 2
ER -
ID: 173778105