A High Throughput Approach for Designing Polymers That Mimic the TRAIL Protein

Title: A High Throughput Approach for Designing Polymers That Mimic the TRAIL Protein
Creator: Li, Zihao; Han, Zifei; Stenzel, Martina H.; Chapman, Robert
Relation: Nano Letters Vol. 22, Issue 7, p. 2660-2666
Publisher Link: http://dx.doi.org/10.1021/acs.nanolett.1c04469
Publisher: American Chemical Society (ACS)
Resource Type: journal article
Date: 2022
Description: We have leveraged a high throughput approach to design a fully synthetic polymer mimic of the chemotherapeutic protein "TRAIL". Our design enables the synthesis of libraries of star-shaped polymers presenting exactly one receptor binding peptide at the end of each arm with no purification steps. Clear structure-activity relationships in screening for receptor binding and the apoptotic activity on colon cancer lines (COLO205) led us to identify trivalent structures, ∼1.5 nm in hydrodynamic radius as the best mimics. These showed IC₅₀ values ∼2 μM and resulted in the elevated levels of caspase-8 expected from this mechanism of cell death. Our results demonstrate the potential for HTP screening methods to be used in the design of polymers that can mimic a whole range of complex therapeutic proteins.
Subject: high throughput screening; TRAIL; protein mimic; controlled radical polymerization; RAFT; SDG 3; Sustainable Development Goals
Identifier: http://hdl.handle.net/1959.13/1482750
Identifier: uon:51014
Identifier: ISSN:1530-6984
Language: eng
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