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Gaining Insights into Specific Drug Formulation Additives for Solubilizing a Potential Anti‐Alzheimer Disease Drug B4A1
Author(s) -
Lawatscheck Carmen,
Pickhardt Marcus,
Grafl Anna,
Linkert Katharina,
Polster Frank,
Mandelkow Eckhard,
Börner Hans G.
Publication year - 2017
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201700109
Subject(s) - drug , peg ratio , chemistry , ethylene glycol , peptide , solubility , combinatorial chemistry , drug carrier , pharmacology , biochemistry , organic chemistry , medicine , finance , economics
The pharmacological profiles of small molecule drugs are often challenged by their poor water solubility. Sequence‐defined peptides attached to poly(ethylene glycol) (PEG) offer opportunities to overcome these difficulties by acting as drug‐specific formulation additives. The peptide‐PEG conjugates enable specific, noncovalent drug binding via tailored peptide/drug interactions as well as provide water solubility and drug shielding by well‐solvated PEG‐blocks. A systematic set of specific solubilizers for B4A1 as a potential anti‐Alzheimer disease drug is synthesized and variations involve the length of the PEG‐blocks as well as the sequences of the peptidic drug‐binding domain. The solubilizer/B4A1 complexes are studied in order to understand contributions of both PEG and peptide segments on drug payload capacities, drug/carrier aggregate sizes, and influences on inhibition of the Tau‐protein aggregation in an in vitro assay.