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Prof. Dr. habil. Hans Börner
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+49 (0)30 2093-7348 |
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+49 (0)30 2093-7500 |
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Contact Us |
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Laboratory for Organic Synthesis of Functional Systems
Department of Chemistry
Humboldt-Universität zu Berlin
Brook-Taylor-Str. 2
12489 Berlin
Germany
Sekretariat
Phone: +49 (0)30 2093-7349
Fax: +49 (0)30 2093-7215
Room: 0'144
Email
office.functional-systems hu-berlin.de
Anfahrt
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News
Fine-tuning Nanocarriers Specifically toward Cargo: A Competitive Study on Solubilizing Related Photosensitizers for Photodynamic Therapy
Full Abstract:Tailor-made drug solubilizers are studied based on peptide-poly(ethylene glycol) conjugates, which exhibit peptide segments constituting binding motifs for the small-molecule drugs of interest to render them water-soluble. Suitable 7mer peptides are selected via combinatorial means by screening large one-bead-one-compound (OBOC) peptide libraries. The capability of the screening method to read out structural detail of the drugs is investigated by comparing three related photosensitizers (Chlorin E6 (Ce6), Pheophorbide A (Pba) and meta-tetra(hydroxyphenyl)chlorin (m-THPC), which are applicable for photodynamic cancer therapy. The screening procedure delivers de novo solubilizers that show the best solubilization efficiency for the drug the screening is performed with. While molecular recognition events between peptide and drug are not expected to be found, significant binding capacity differences of, e.g., the Ce6-solubilizer for Pba are suggesting selectivity in drug binding, even among structurally closely related drugs. Cyro-Electron microscopy revealed the formation of colloidal aggregates between drug moieties and peptide conjugates. Insights into relevant amino acids in the identified peptide sequences are gained by studying capacities of systematic point mutations (alanine scans), enabling understanding of drug-binding motifs. These reveal the importance of sequence positioning of appropriate H-bonding between polar functional groups of the peptide and the drugs, which agrees well with computational binding studies performed on drug/peptide model complexes.
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