PMID: 11929232Apr 4, 2002Paper

A modular assembly strategy for improving the substrate specificity of small catalytic peptides

Journal of the American Chemical Society
Fujie Tanaka, C F Barbas

Abstract

In contrast to large proteins, small peptide catalysts typically display limited specificity for small molecule substrates. This is presumably a result of the limited opportunities small peptides have to fold in a manner that provides for the formation of an isolated reaction vessel that effectively binds and sequesters substrates from bulk solvent while at the same time catalyzing their transformation. For the preparation of small peptide catalysts that possess improved substrate specificity, we have developed a modular assembly strategy that involves appending phage display-derived substrate binding-domain modules to catalytically active peptide domains. We demonstrate the potential of this strategy with the construction of a small 35-amino acid residue aldolase peptide with improved substrate specificity. The advantages of this approach are that it reduces the demand on the functionalization of the catalytic site and it is modular, therefore making its adaptation to a variety of specificities rapid. The modular assembly strategy studied here may present advantages over exhaustive searches of large random-sequence peptide libraries for peptides with singular function.

References

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Citations

Oct 8, 2005·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Fujie Tanaka
Nov 25, 2003·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Kristi L Burns, Sheldon W May
Dec 31, 2003·Journal of Molecular Biology·Fujie TanakaCarlos F Barbas
Jul 3, 2007·Bioconjugate Chemistry·Fujie TanakaCarlos F Barbas
Sep 21, 2012·Journal of the American Chemical Society·Mahboubeh KheirabadiChristian E Schafmeister
Feb 19, 2009·The Journal of Organic Chemistry·Hai-Ming Guo, Fujie Tanaka
Jul 5, 2005·Nature Reviews. Genetics·Steven A Benner, A Michael Sismour
Mar 8, 2008·Science·Lin JiangDavid Baker
Oct 29, 2013·Journal of Molecular Biology·Sinisa BjelicDavid Baker
Jun 6, 2007·Current Opinion in Chemical Biology·Jefferson D Revell, Helma Wennemers
Apr 16, 2013·Biochimie·Jaroslav KubrychtJiří Hudeček
Sep 25, 2004·Bioorganic & Medicinal Chemistry·Yang XuKim D Janda
Mar 6, 2015·Organic & Biomolecular Chemistry·Palwinder SinghAmrinder Singh
Mar 27, 2018·Angewandte Chemie·Chi ZhangBradley L Pentelute
Sep 27, 2006·Angewandte Chemie·Andrew P BroganKim D Janda
Mar 21, 2006·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Axel HundingRobert Root-Bernstein
Jul 10, 2003·Journal of the American Chemical Society·Fujie TanakaCarlos F Barbas
Dec 6, 2003·The Journal of Organic Chemistry·Wolfgang NotzCarlos F Barbas

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