An Array-Based Ligand Discovery Platform for Proteins With Short Half-Lives.

Methods Enzymol
Authors
Keywords
Abstract

Many promising therapeutic protein targets were previously considered "undruggable" due to a deficit in structural information to guide drug design and/or a lack of an obvious binding pocket. Fortunately, array-based methods for evaluating protein binding against large chemical libraries, such as small-molecule microarray screening, have provided one of several emerging inroads to ligand discovery for these elusive targets. Despite the advance in the area of ligand discovery for poorly structured and intrinsically disordered proteins provided by array-based technologies involving cell lysates, the extension of this technology for screening proteins with short half-lives in physiologically relevant conformations has been technically challenging. In this chapter we present a protocol for leveraging in vitro translation strategies to enable array-based screening of short-lived proteins against large small-molecule libraries for ligand discovery.

Year of Publication
2018
Journal
Methods Enzymol
Volume
610
Pages
191-218
Date Published
2018
ISSN
1557-7988
DOI
10.1016/bs.mie.2018.09.019
PubMed ID
30390799
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