Generalizing the Concept of Specific Compound Formulation Additives towards Non-Fluorescent Drugs: A Solubilization Study on Potential Anti-Alzheimer-Active Small-Molecule Compounds.
Tailor-made compound formulation additives enable the testing of potential drugs with undesirable pharmacological profiles. A combinatorial approach using Raman microscopy as the readout method is presented to select peptide sequences from large one-bead-one-compound libraries. The resulting peptide-PEG conjugates solubilize potential prophylactic and therapeutic anti-Alzheimer compounds and can be used as specific additives not only for fluorescent but also for non-fluorescent compounds.
Humboldt-Universität zu Berlin, Department of Chemistry, Brook-Taylor-Strasse 2, 12489, Berlin, Germany.
Carmen
C
Lawatscheck
German Center for Neurodegenerative Diseases (DZNE), CAESAR Research Center, Ludwig-Erhard-Allee 2, 53175, Bonn, Germany.
Marcus
M
Pickhardt
Humboldt-Universität zu Berlin, Department of Chemistry, Brook-Taylor-Strasse 2, 12489, Berlin, Germany.
Sebastian
S
Wieczorek
Max Planck Institute of Colloids and Interfaces, Department of Theory and Biosystems, Am Mühlenberg 1, 14476, Potsdam, Germany.
Andrea
A
Grafmüller
German Center for Neurodegenerative Diseases (DZNE), CAESAR Research Center, Ludwig-Erhard-Allee 2, 53175, Bonn, Germany.|MPI for Metabolism Research, Hamburg Outstation, c/o DESY, Notkestrasse 85, 22607, Hamburg, Germany.
Eckhard
E
Mandelkow
Humboldt-Universität zu Berlin, Department of Chemistry, Brook-Taylor-Strasse 2, 12489, Berlin, Germany. h.boerner@HU-Berlin.de.
Hans G
HG
Börner
D000544:Alzheimer Disease / Q000188:drug therapy; D015195:Drug Design; D000067493:Dynamic Light Scattering; D006801:Humans; D008853:Microscopy; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D066329:Protein Aggregates / Q000187:drug effects; D011485:Protein Binding; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D012995:Solubility; D013059:Spectrum Analysis, Raman; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism
D019151:Peptide Library; D010455:Peptides; D066329:Protein Aggregates; D054852:Small Molecule Libraries; D016875:tau Proteins; D011092:Polyethylene Glycols
Alzheimer's disease; Tau protein; bioconjugates; combinatorial screening; precision polymers