Specific Drug Formulation Additives: Revealing the Impact of Architecture and Block Length Ratio

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.