Self‐Immolative Activation of β‐Galactosidase‐Responsive Probes for In Vivo MR Imaging in Mouse Models
Abstract Our lab has developed a new series of self‐immolative MR agents for the rapid detection of enzyme activity in mouse models expressing β‐galactosidase (β‐gal). We investigated two molecular architectures to create agents that detect β‐gal activity by modulating the coordination of water to Gd III. The first is an intermolecular approach, wherein we designed several structural isomers to maximize coordination of endogenous carbonate ions. The second involves an intramolecular mechanism for q modulation. We incorporated a pendant coordinating carboxylate ligand with a 2, 4, 6, or 8 carbon linker to saturate ligand coordination to the Gd III ion. This renders the agent ineffective. We show that one agent in particular (6‐C pendant carboxylate) is an extremely effective MR reporter for the detection of enzyme activity in a mouse model expressing β‐gal..
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:59 |
|---|---|
| Enthalten in: |
Angewandte Chemie International Edition - 59(2020), 1, Seite 388-394 |
| Beteiligte Personen: |
Lilley, Laura M. [VerfasserIn] |
|---|
| BKL: |
|---|
| Anmerkungen: |
© 2020 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim |
|---|
| Umfang: |
7 |
|---|
| doi: |
10.1002/anie.201909933 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
WLY001967495 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | WLY001967495 | ||
| 003 | DE-627 | ||
| 005 | 20230307112102.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230210s2020 xx |||||o 00| ||und c | ||
| 024 | 7 | |a 10.1002/anie.201909933 |2 doi | |
| 028 | 5 | 2 | |a ANIE_ANIE201909933.xml |
| 035 | |a (DE-627)WLY001967495 | ||
| 035 | |a (WILEY)ANIE201909933 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 082 | 0 | 4 | |a 540 |q ASE |
| 082 | 0 | 4 | |a 540 |q ASE |
| 084 | |a 35.00 |2 bkl | ||
| 100 | 1 | |a Lilley, Laura M. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Self‐Immolative Activation of β‐Galactosidase‐Responsive Probes for In Vivo MR Imaging in Mouse Models |
| 264 | 1 | |c 2020 | |
| 300 | |a 7 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a © 2020 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim | ||
| 520 | |a Abstract Our lab has developed a new series of self‐immolative MR agents for the rapid detection of enzyme activity in mouse models expressing β‐galactosidase (β‐gal). We investigated two molecular architectures to create agents that detect β‐gal activity by modulating the coordination of water to Gd III. The first is an intermolecular approach, wherein we designed several structural isomers to maximize coordination of endogenous carbonate ions. The second involves an intramolecular mechanism for q modulation. We incorporated a pendant coordinating carboxylate ligand with a 2, 4, 6, or 8 carbon linker to saturate ligand coordination to the Gd III ion. This renders the agent ineffective. We show that one agent in particular (6‐C pendant carboxylate) is an extremely effective MR reporter for the detection of enzyme activity in a mouse model expressing β‐gal. | ||
| 700 | 1 | |a Kamper, Sarah |4 aut | |
| 700 | 1 | |a Caldwell, Michael |4 aut | |
| 700 | 1 | |a Chia, Zer Keen |4 aut | |
| 700 | 1 | |a Ballweg, David |4 aut | |
| 700 | 1 | |a Vistain, Luke |4 aut | |
| 700 | 1 | |a Krimmel, Jeffrey |4 aut | |
| 700 | 1 | |a Mills, Teresa Anne |4 aut | |
| 700 | 1 | |a MacRenaris, Keith |4 aut | |
| 700 | 1 | |a Lee, Paul |4 aut | |
| 700 | 1 | |a Waters, Emily Alexandria |4 aut | |
| 700 | 1 | |a Meade, Thomas J. |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Angewandte Chemie International Edition |g 59(2020), 1, Seite 388-394 |w (DE-627)WLY001913387 |x 15213773 |7 nnns |
| 773 | 1 | 8 | |g volume:59 |g year:2020 |g number:1 |g pages:388-394 |g extent:7 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_WLY | ||
| 936 | b | k | |a 35.00 |q ASE |
| 951 | |a AR | ||
| 952 | |d 59 |j 2020 |e 1 |h 388-394 |g 7 | ||