Details
| Original language | English |
|---|---|
| Pages (from-to) | 1507-1514 |
| Number of pages | 8 |
| Journal | Bioconjugate Chemistry |
| Volume | 24 |
| Issue number | 9 |
| Early online date | 22 Aug 2013 |
| Publication status | Published - 18 Sept 2013 |
| Externally published | Yes |
Abstract
Herein we describe a platform technology for the synthesis and characterization of partially aminated, 35S-labeled, dendritic polyglycerol sulfate (dPG35S amine) and fluorescent dPGS indocarbocyanine (ICC) dye conjugates. These polymer conjugates, based on a biocompatible dendritic polyglycerol scaffold, exhibit a high affinity to inflamed tissue in vivo and represent promising candidates for therapeutic and diagnostic applications. By utilizing a one-step sequential copolymerization approach, dendritic polyglycerol (Mn ≈ 4.5 kDa) containing 9.4% N-phthalimide protected amine functionalities was prepared on a large scale. Sulfation and simultaneous radio labeling with 35SO3 pyridine complex, followed by cleavage of the N-phthalimide protecting groups, yielded dPG35S amine as a beta emitting, inflammation specific probe with free amino functionalities for conjugation. Furthermore, efficient labeling procedures with ICC via iminothiolane modification and subsequent "Michael" addition of the maleimide functionalized ICC dye, as well as by amide formation via NHS derivatized ICC on a dPGS amine scaffold, are described. The dPGS-ICC conjugates were investigated with respect to their photophysical properties, and both the radiolabeled and fluorescent compounds were comparatively visualized in histological tissue sections (radio detection and fluorescence microscopy) of animals treated with dPGS. Furthermore, cellular uptake of dPGS-ICC was found in endothelial cord blood (HUVEC) and the epithelial lung cells (A549). The presented synthetic routes allow a reproducible, controlled synthesis of dPGS amine on kilogram scale applying a one-pot batch reaction process. dPGS amine can be used for analysis via radioactivity or fluorescence, thereby creating a new platform for inflammation specific, multimodal imaging purposes using other attachable probes or contrast agents.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biotechnology
- Chemical Engineering(all)
- Bioengineering
- Engineering(all)
- Biomedical Engineering
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmacology
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmaceutical Science
- Chemistry(all)
- Organic Chemistry
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In: Bioconjugate Chemistry, Vol. 24, No. 9, 18.09.2013, p. 1507-1514.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Synthesis and biological evaluation of radio and dye labeled amino functionalized dendritic polyglycerol sulfates as multivalent anti-inflammatory compounds
AU - Gröger, Dominic
AU - Paulus, Florian
AU - Licha, Kai
AU - Welker, Pia
AU - Weinhart, Marie
AU - Holzhausen, Cornelia
AU - Mundhenk, Lars
AU - Gruber, Achim D.
AU - Abram, Ulrich
AU - Haag, Rainer
PY - 2013/9/18
Y1 - 2013/9/18
N2 - Herein we describe a platform technology for the synthesis and characterization of partially aminated, 35S-labeled, dendritic polyglycerol sulfate (dPG35S amine) and fluorescent dPGS indocarbocyanine (ICC) dye conjugates. These polymer conjugates, based on a biocompatible dendritic polyglycerol scaffold, exhibit a high affinity to inflamed tissue in vivo and represent promising candidates for therapeutic and diagnostic applications. By utilizing a one-step sequential copolymerization approach, dendritic polyglycerol (Mn ≈ 4.5 kDa) containing 9.4% N-phthalimide protected amine functionalities was prepared on a large scale. Sulfation and simultaneous radio labeling with 35SO3 pyridine complex, followed by cleavage of the N-phthalimide protecting groups, yielded dPG35S amine as a beta emitting, inflammation specific probe with free amino functionalities for conjugation. Furthermore, efficient labeling procedures with ICC via iminothiolane modification and subsequent "Michael" addition of the maleimide functionalized ICC dye, as well as by amide formation via NHS derivatized ICC on a dPGS amine scaffold, are described. The dPGS-ICC conjugates were investigated with respect to their photophysical properties, and both the radiolabeled and fluorescent compounds were comparatively visualized in histological tissue sections (radio detection and fluorescence microscopy) of animals treated with dPGS. Furthermore, cellular uptake of dPGS-ICC was found in endothelial cord blood (HUVEC) and the epithelial lung cells (A549). The presented synthetic routes allow a reproducible, controlled synthesis of dPGS amine on kilogram scale applying a one-pot batch reaction process. dPGS amine can be used for analysis via radioactivity or fluorescence, thereby creating a new platform for inflammation specific, multimodal imaging purposes using other attachable probes or contrast agents.
AB - Herein we describe a platform technology for the synthesis and characterization of partially aminated, 35S-labeled, dendritic polyglycerol sulfate (dPG35S amine) and fluorescent dPGS indocarbocyanine (ICC) dye conjugates. These polymer conjugates, based on a biocompatible dendritic polyglycerol scaffold, exhibit a high affinity to inflamed tissue in vivo and represent promising candidates for therapeutic and diagnostic applications. By utilizing a one-step sequential copolymerization approach, dendritic polyglycerol (Mn ≈ 4.5 kDa) containing 9.4% N-phthalimide protected amine functionalities was prepared on a large scale. Sulfation and simultaneous radio labeling with 35SO3 pyridine complex, followed by cleavage of the N-phthalimide protecting groups, yielded dPG35S amine as a beta emitting, inflammation specific probe with free amino functionalities for conjugation. Furthermore, efficient labeling procedures with ICC via iminothiolane modification and subsequent "Michael" addition of the maleimide functionalized ICC dye, as well as by amide formation via NHS derivatized ICC on a dPGS amine scaffold, are described. The dPGS-ICC conjugates were investigated with respect to their photophysical properties, and both the radiolabeled and fluorescent compounds were comparatively visualized in histological tissue sections (radio detection and fluorescence microscopy) of animals treated with dPGS. Furthermore, cellular uptake of dPGS-ICC was found in endothelial cord blood (HUVEC) and the epithelial lung cells (A549). The presented synthetic routes allow a reproducible, controlled synthesis of dPGS amine on kilogram scale applying a one-pot batch reaction process. dPGS amine can be used for analysis via radioactivity or fluorescence, thereby creating a new platform for inflammation specific, multimodal imaging purposes using other attachable probes or contrast agents.
UR - http://www.scopus.com/inward/record.url?scp=84884407924&partnerID=8YFLogxK
U2 - 10.1021/bc400047f
DO - 10.1021/bc400047f
M3 - Article
C2 - 23924212
AN - SCOPUS:84884407924
VL - 24
SP - 1507
EP - 1514
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
SN - 1043-1802
IS - 9
ER -