In situ click chemistry: from small molecule discovery to synthetic antibodies
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 d...
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| Published in: | Integrative biology (Cambridge) Vol. 5; no. 1; pp. 87 - 95 |
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| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
England
01-01-2013
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | 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.
Iterative
in situ
click chemistry provides a route to novel mutli-peptide ligands with antibody-like affinity and specificity. |
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| Bibliography: | Dr Heather Agnew earned bachelor's degrees in chemistry and BMB (2003) from Penn State University. As a Gates Scholar, she received an MPhil in chemistry (2005) from University of Cambridge. Heather went on to study under Professor James R. Heath at Caltech, where she received the Lemelson-MIT Caltech Student Prize for her role in developing techniques to create synthetic, site-specific binding molecules as alternatives to antibodies. After receiving her PhD (2010), Heather joined Integrated Diagnostics, where she leads a program focused on commercialization of PCC Agents. She holds an adjunct appointment in the David Geffen School of Medicine at UCLA. Dr Steven Millward grew up just south of Pittsburgh, Pennsylvania and received his Bachelors of Arts in Biology in 2000 from The Johns Hopkins University. His graduate work in molecular evolution at The California Institute of Technology was carried out under the supervision of Richard W. Roberts. He continued his studies at Caltech as a postdoc with James Heath where he employed in situ click chemistry to design branched peptide kinase inhibitors. He is currently developing new experimental compounds for targeted molecular imaging of cancer as an assistant professor at the University of Texas MD Anderson Cancer Center. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-2 |
| ISSN: | 1757-9694 1757-9708 1757-9708 |
| DOI: | 10.1039/c2ib20110k |