Details
| Original language | English |
|---|---|
| Pages (from-to) | 383-388 |
| Number of pages | 6 |
| Journal | Bioconjugate chemistry |
| Volume | 26 |
| Issue number | 3 |
| Publication status | Published - 28 Jan 2015 |
| Externally published | Yes |
Abstract
(Graph Presented). Targeted drug-delivery methods are crucial for effective treatment of degenerative joint diseases such as osteoarthritis (OA). Toward this goal, we developed a small multivalent structure as a model drug for the attenuation of cartilage degradation. The DOTAM (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid amide)-based model structure is equipped with the cathepsin D protease inhibitor pepstatin A, a fluorophore, and peptide moieties targeting collagen II. In vivo injection of these soluble probes into the knee joints of mice resulted in 7-day-long local retention, while the drug carrier equipped with a scrambled peptide sequence was washed away within 6-8 h. The model drug conjugate successfully reduced the cathepsin D protease activity as measured by release of GAG peptide. Therefore, these conjugates represent a promising first drug conjugate for the targeted treatment of degenerative joint diseases.
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. 26, No. 3, 28.01.2015, p. 383-388.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - DOTAM Derivatives as Active Cartilage-Targeting Drug Carriers for the Treatment of Osteoarthritis
AU - Hu, Hai Yu
AU - Lim, Ngee Han
AU - Ding-Pfennigdorff, Danping
AU - Saas, Joachim
AU - Wendt, K. Ulrich
AU - Ritzeler, Olaf
AU - Nagase, Hideaki
AU - Plettenburg, Oliver
AU - Schultz, Carsten
AU - Nazare, Marc
PY - 2015/1/28
Y1 - 2015/1/28
N2 - (Graph Presented). Targeted drug-delivery methods are crucial for effective treatment of degenerative joint diseases such as osteoarthritis (OA). Toward this goal, we developed a small multivalent structure as a model drug for the attenuation of cartilage degradation. The DOTAM (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid amide)-based model structure is equipped with the cathepsin D protease inhibitor pepstatin A, a fluorophore, and peptide moieties targeting collagen II. In vivo injection of these soluble probes into the knee joints of mice resulted in 7-day-long local retention, while the drug carrier equipped with a scrambled peptide sequence was washed away within 6-8 h. The model drug conjugate successfully reduced the cathepsin D protease activity as measured by release of GAG peptide. Therefore, these conjugates represent a promising first drug conjugate for the targeted treatment of degenerative joint diseases.
AB - (Graph Presented). Targeted drug-delivery methods are crucial for effective treatment of degenerative joint diseases such as osteoarthritis (OA). Toward this goal, we developed a small multivalent structure as a model drug for the attenuation of cartilage degradation. The DOTAM (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid amide)-based model structure is equipped with the cathepsin D protease inhibitor pepstatin A, a fluorophore, and peptide moieties targeting collagen II. In vivo injection of these soluble probes into the knee joints of mice resulted in 7-day-long local retention, while the drug carrier equipped with a scrambled peptide sequence was washed away within 6-8 h. The model drug conjugate successfully reduced the cathepsin D protease activity as measured by release of GAG peptide. Therefore, these conjugates represent a promising first drug conjugate for the targeted treatment of degenerative joint diseases.
UR - http://www.scopus.com/inward/record.url?scp=84924963057&partnerID=8YFLogxK
U2 - 10.1021/bc500557s
DO - 10.1021/bc500557s
M3 - Article
C2 - 25629889
AN - SCOPUS:84924963057
VL - 26
SP - 383
EP - 388
JO - Bioconjugate chemistry
JF - Bioconjugate chemistry
SN - 1043-1802
IS - 3
ER -