A dual-functional peptide probe for simutaneous stem cell monitoring and restoring
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1
School of Dentistry, Seoul National University, Department of Dental Regenerative Biotechnology, Korea
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2
Nano Intelligent Biomedical Engineering Corporation (NIBEC), Central Research Institute, Korea
Simultaneous diagnostic imaging and therapy for targeting diseases has relied on the specific enzymatic activity opposed to a substrate target molecule as well as the sensitivity of probing dyes. Because target enzyme-proteins as substrates interaction is occurred first, however, the probe design should be considered on the basis of protein-protein binding concepts. Here, an E3 ubiquitin ligase was used as a protein binding target. The ubiquitin-proteasome system (UPS) is a natural protein degradation process to remove abnormal proteins that has involved in many diseases. In biomineralization, Smad1/5/8 have been known as key molecules. The molecules can be irreversibly removed by Smurf1, a HECT class ubiquitin ligase in UPS that inhibits osteoblast differentiation. Herein, we designed the peptide probe by conjugating a fluorescent dye and a black hole quencher, leading to re-emission of quenched probe as soon as binding with its intracellular target. Simultaneously, the degradation of Smad 1/5/8 by Smurf1-our peptide probe interaction can induce osteogenesis in parallel with increasing the expression of several osteo-inductive genes. Therefore, the peptide probe can be applied for affinity-based imaging and treatment both cells and animals, in which can be performed with real-time monitoring of a processed stage in Smurf1-overexpressing diseases such as rheumatic arthritis, osteoporosis and cancers.
This work was supported in part by the Bio & Medical Technology Development Program (#2012049727) and in part by the Oromaxillofacial Dysfunction Research Center for the Elderly ar Seoul National University in Korea (#2012000912) of the National Research Foundation (NRF) funded by the Ministry of Science, ICT, and Future Planning.
References:
[1] Sangadala S, Boden SD, Metpally RP, Reddy BV. “Modeling and analysis of molecular interaction between Smurf1-WW2 domain and various isoforms of LIM mineralization protein.”, Proteins. 68:690-701 (2007).
[2] Park YJ, Chang LC, Liang JF, Moon C, Chung CP, Yang VC, “Nontoxic membrane translocation peptide from protamine, low molecular weight protamine (LMWP)”, for enhanced intracellular protein delivery: in vitro and in vivo study. FASEB J 19:1555-1557, (2005).
Keywords:
Bone Regeneration,
Molecular Imaging,
theranostic,
Bioactive molecule
Conference:
10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.
Presentation Type:
Poster
Topic:
Cell-targeting biomaterials in theranostic delivery
Citation:
Suh
J,
Lee
J,
Chung
C and
Park
Y
(2016). A dual-functional peptide probe for simutaneous stem cell monitoring and restoring.
Front. Bioeng. Biotechnol.
Conference Abstract:
10th World Biomaterials Congress.
doi: 10.3389/conf.FBIOE.2016.01.00470
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Received:
27 Mar 2016;
Published Online:
30 Mar 2016.