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In situ click chemistry: from small molecule discovery to synthetic antibodies

Millward, Steven W. and Agnew, Heather D. and Lai, Bert T. and Lee, Su Seong and Lim, Jaehong and Nag, Arundhati and Pitram, Suresh and Rohde, Rosemary and Heath, James R. (2013) In situ click chemistry: from small molecule discovery to synthetic antibodies. Integrative Biology, 5 (1). pp. 87-95. ISSN 1757-9694. doi:10.1039/C2IB20110K.

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Advances in the fields of proteomics, molecular imaging, and therapeutics are closely linked to the availability of affinity reagents that selectively recognize their biological targets. Here we present a review of Iterative Peptide In Situ Click Chemistry (IPISC), a novel screening technology for designing peptide multiligands with high affinity and specificity. This technology builds upon in situ click chemistry, a kinetic target-guided synthesis approach where the protein target catalyzes the conjugation of two small molecules, typically through the azide–alkyne Huisgen cycloaddition. Integrating this methodology with solid phase peptide libraries enables the assembly of linear and branched peptide multiligands we refer to as Protein Catalyzed Capture Agents (PCC Agents). The resulting structures can be thought of as analogous to the antigen recognition site of antibodies and serve as antibody replacements in biochemical and cell-based applications. In this review, we discuss the recent progress in ligand design through IPISC and related approaches, focusing on the improvements in affinity and specificity as multiligands are assembled by target-catalyzed peptide conjugation. We compare the IPISC process to small molecule in situ click chemistry with particular emphasis on the advantages and technical challenges of constructing antibody-like PCC Agents.

Item Type:Article
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URLURL TypeDescription CentralArticle
Heath, James R.0000-0001-5356-4385
Additional Information:© 2013 Royal Society of Chemistry. Received 5th May 2012, Accepted 5th July 2012. First published on the web 26 Jul 2012. This work was supported by the Institute for Collaborative Biotechnologies through grant W911NF-09-0001 from the U.S. Army Research Office and by the Institute of Bioengineering and Nanotechnology (Biomedical Research Council, Agency for Science, Technology and Research, Singapore) and by the National Cancer Institute Grant No. 5U54 CA119347 (JRH). SWM acknowledges support from an NRSF postdoctoral fellowship 1F32CA13615001.
Funding AgencyGrant Number
Army Research Office (ARO)W911NF-09-0001
Agency for Science, Technology and Research (A*STAR)UNSPECIFIED
National Cancer Institute5U54 CA119347
NIH Postdoctoral Fellowship1F32CA13615001
Issue or Number:1
Record Number:CaltechAUTHORS:20130117-072805253
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Official Citation:In situ click chemistry: from small molecule discovery to synthetic antibodies Steven W. Millward, Heather D. Agnew, Bert Lai, Su Seong Lee, Jaehong Lim, Arundhati Nag, Suresh Pitram, Rosemary Rohde and James R. Heath Integr. Biol., 2013, 5, 87-95 DOI: 10.1039/C2IB20110K
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:36438
Deposited By: Ruth Sustaita
Deposited On:17 Jan 2013 16:25
Last Modified:09 Nov 2021 23:22

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