title: Specific Drug Formulation Additives: Revealing the Impact of Architecture and Block Length Ratio.
abstract: Combining poly(ethylene glycol) (PEG) with sequence-defined peptides in PEG-peptide conjugates offers opportunities to realize next-generation drug formulation additives for overcoming undesired pharmacological profiles of difficult small molecule drugs. The tailored peptide segments provide sequence-specific, noncovalent drug binding, and the hydrophilic PEG block renders the complexes water soluble. On the basis of a peptide sequence known to bind the photosensitizer m-tetra(hydroxyphenyl)chlorin (m-THPC) for photodynamic cancer therapy, a set of different conjugate architectures is synthesized and studied. Variations in PEG block length and amplification of the peptidic binding domain of PEG-peptide conjugates are used to fine tune critical parameters for hosting m-THPC, such as drug payload capacities, aggregation sizes, and drug release and activation kinetics.
authors: Department of Chemistry, Laboratory for Organic Synthesis of Functional Systems, Humboldt-Universität zu Berlin , Brook-Taylor-Str. 2, D-12489 Berlin, Germany.
authors: Sebastian
authors: S
authors: Wieczorek
authors: Department of Chemistry, Laboratory for Organic Synthesis of Functional Systems, Humboldt-Universität zu Berlin , Brook-Taylor-Str. 2, D-12489 Berlin, Germany.
authors: Timm
authors: T
authors: Schwaar
authors: School of Chemistry, SFI Tetrapyrrole Laboratory, Trinity Biomedical Sciences Institute, Trinity College Dublin, The University of Dublin , 152-160 Pearse Street, Dublin, 2, Ireland.
authors: Mathias O
authors: MO
authors: Senge
authors: Department of Chemistry, Laboratory for Organic Synthesis of Functional Systems, Humboldt-Universität zu Berlin , Brook-Taylor-Str. 2, D-12489 Berlin, Germany.
authors: Hans G
authors: HG
authors: Börner
mesh_terms: D002626:Chemistry, Pharmaceutical; D010455:Peptides / Q000737:chemistry*; D017319:Photosensitizing Agents / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013056:Spectrophotometry, Ultraviolet
chemical_list: D010455:Peptides; D017319:Photosensitizing Agents; D011092:Polyethylene Glycols