特定药物制剂添加剂：揭示结构和嵌段长度比的影响
Specific Drug Formulation Additives: Revealing the Impact of Architecture and Block Length Ratio.
作者信息
Wieczorek Sebastian, Schwaar Timm, Senge Mathias O, Börner Hans G
机构信息
Department of Chemistry, Laboratory for Organic Synthesis of Functional Systems, Humboldt-Universität zu Berlin , Brook-Taylor-Str. 2, D-12489 Berlin, Germany.
School of Chemistry, SFI Tetrapyrrole Laboratory, Trinity Biomedical Sciences Institute, Trinity College Dublin, The University of Dublin , 152-160 Pearse Street, Dublin, 2, Ireland.
出版信息
Biomacromolecules. 2015 Oct 12;16(10):3308-12. doi: 10.1021/acs.biomac.5b00961. Epub 2015 Sep 10.
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.
将聚乙二醇（PEG）与聚乙二醇-肽缀合物中序列确定的肽相结合，为实现下一代药物制剂添加剂提供了机会，以克服难溶性小分子药物不良的药理学特性。定制的肽段提供序列特异性的非共价药物结合，而亲水性PEG嵌段使复合物具有水溶性。基于已知可结合用于光动力癌症治疗的光敏剂间四（羟苯基）氯卟啉（m-THPC）的肽序列，合成并研究了一组不同的缀合物结构。利用PEG嵌段长度的变化和PEG-肽缀合物肽结合域的扩增来微调容纳m-THPC的关键参数，如药物负载能力、聚集大小以及药物释放和活化动力学。
Zotero 插件