Tumor Targeting with an iso DGR–Drug Conjugate
Abstract Herein we report the first example of an iso DGR–drug conjugate ( 2 ), designed to release paclitaxel selectively within cancer cells expressing integrin α V β 3 . Conjugate 2 was synthesized by connecting the iso DGR peptidomimetic 5 with paclitaxel via the lysosomally cleavable Val–Ala di...
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Published in | Chemistry : a European journal Vol. 23; no. 33; pp. 7910 - 7914 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
12.06.2017
|
Online Access | Get full text |
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Summary: | Abstract
Herein we report the first example of an
iso
DGR–drug conjugate (
2
), designed to release paclitaxel selectively within cancer cells expressing integrin α
V
β
3
. Conjugate
2
was synthesized by connecting the
iso
DGR peptidomimetic
5
with paclitaxel via the lysosomally cleavable Val–Ala dipeptide linker. Conjugate
2
displayed a low nanomolar affinity for the purified integrin α
V
β
3
receptor (IC
50
=11.0 n
m
). The tumor targeting ability of conjugate
2
was assessed in vitro in anti‐proliferative assays on two isogenic cancer cell lines characterized by different integrin α
V
β
3
expression: human glioblastoma U87 (α
V
β
3
+) and U87 β
3
‐KO (α
V
β
3
−). The
iso
DGR‐PTX conjugate
2
displayed a remarkable targeting index (TI=9.9), especially when compared to the strictly related RGD‐PTX conjugate
4
(TI=2.4). |
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ISSN: | 0947-6539 1521-3765 |
DOI: | 10.1002/chem.201701844 |