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New p32/gC1qR Ligands for Targeted Tumor Drug Delivery
Author(s) -
Paasonen Lauri,
Sharma Shweta,
Braun Gary B.,
Kotamraju Venkata Ramana,
Chung Thomas D. Y.,
She ZhiGang,
Sugahara Kazuki N.,
Yliperttula Marjo,
Wu Bainan,
Pellecchia Maurizio,
Ruoslahti Erkki,
Teesalu Tambet
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201500564
Subject(s) - peptide , chemistry , in vivo , drug delivery , drug , lead compound , targeted drug delivery , peptide library , combinatorial chemistry , biophysics , in vitro , biochemistry , peptide sequence , pharmacology , biology , microbiology and biotechnology , organic chemistry , gene
Cell surface p32, the target of LyP‐1 homing peptide, is upregulated in tumors and atherosclerotic plaques and has been widely used as a receptor for systemic delivery of payloads. Here, we identified an improved LyP‐1‐mimicking peptide (TT1, CKRGARSTC). We used this peptide in a fluorescence polarization‐based high‐throughput screening of a 50 000‐compound chemical library and identified a panel of compounds that bind p32 with low micromolar affinity. Among the hits identified in the screen, two compounds were shown to specifically bind to p32 in multiple assays. One of these compounds was chosen for an in vivo study. Nanoparticles surface‐functionalized with this compound specifically adhered to surfaces coated with recombinant p32 and, when injected intravenously, homed to p32‐expressing breast tumors in mice. This compound provides a lead for the development of p32‐targeted affinity ligands that circumvent some of the limitations of peptide‐based probes in guided drug delivery.