Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2

Nature
Pierre ColasR Brent

Abstract

A network of interacting proteins controls the activity of cyclin-dependent kinase 2 (Cdk2) (refs 1,2) and governs the entry of higher eukaryotic cells into S phase. Analysis of this and other genetic regulatory networks would be facilitated by intracellular reagents that recognize specific targets and inhibit specific network connections. We report here the expression of a combinatorial library of constrained 20-residue peptides displayed by the active-site loop of Escherichia coli thioredoxin, and the use of a two-hybrid system to select those that bind human Cdk2. These peptide aptamers were designed to mimic the recognition function of the complementarity-determining regions of immunoglobulins. The aptamers recognized different epitopes on the Cdk2 surface with equilibrium dissociation constant in the nanomolar range; those tested inhibited Cdk2 activity. Our results show that peptide aptamers bear some analogies with monoclonal antibodies, with the advantages that they are isolated together with their coding genes, that their small size should allow their structures to be solved, and that they are designated to function inside cells.

References

May 1, 1992·Molecular Biology of the Cell·D DesaiD O Morgan
Mar 25, 1992·Nucleic Acids Research·D GietzR H Schiestl
Jun 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·K R OldenburgM A Gallop
Jul 1, 1992·Molecular and Cellular Biology·E A Golemis, R Brent
Aug 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·S E CwirlaW J Dower
Oct 1, 1995·Molecular and Cellular Biology·J EstojakE A Golemis
Apr 11, 1995·Nucleic Acids Research·M YangS Fields
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·R L Finley, R Brent
Dec 30, 1994·Gene·S J McConnellR H Hoess
Mar 9, 1995·Nature·D O Morgan
Nov 18, 1994·Cell·C J Sherr
Jun 15, 1993·Gene·M A McLaffertyW Markland

❮ Previous
Next ❯

Citations

Aug 10, 2000·Journal of Molecular Recognition : JMR·A Skerra
Oct 10, 2001·Angewandte Chemie·Sean V. TaylorDonald Hilvert
Jan 27, 2000·Cell·R Brent
Sep 2, 2003·Trends in Biotechnology·Joachim F Uhrig
Aug 28, 1998·Trends in Biotechnology·P Colas, R Brent
Aug 26, 1999·Trends in Biotechnology·M Vidal, H Endoh
Aug 2, 2003·Journal of Biotechnology·Giordano CaponigroAlexander Kamb
Apr 1, 1998·Trends in Genetics : TIG·A Porter
Apr 11, 2001·Human Immunology·M N'cho, Z Brahmi
Jan 11, 2000·Research in Microbiology·D Ladant, G Karimova
Oct 1, 1996·Current Opinion in Biotechnology·D S McNabb, L Guarente
Apr 21, 1999·Current Opinion in Biotechnology·E V ShustaK D Wittrup
Mar 11, 1999·Current Opinion in Genetics & Development·M D Garrett, A Fattaey
Aug 1, 1997·Current Opinion in Structural Biology·P Kast, D Hilvert
Mar 11, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·M D Garrett, P Workman
Sep 22, 2001·The Journal of Steroid Biochemistry and Molecular Biology·F Hoppe-SeylerK Butz
Jan 5, 1999·Bioorganic & Medicinal Chemistry Letters·X ZangY H Chu
Jun 19, 2002·Trends in Biochemical Sciences·Thomas Kodadek
Feb 5, 2003·Drug Discovery Today·Tweeny R Kau, Pamela A Silver
Feb 17, 2000·Drug Discovery Today·I LofererI Seizinger
Feb 13, 2001·Current Opinion in Chemical Biology·A Kamb, G Caponigro
Feb 19, 2000·Current Opinion in Chemical Biology·P Colas
Jan 5, 2002·Current Opinion in Pharmacology·W James
Jul 14, 2012·Analytical Chemistry·Anthony JohnsonJason J Davis
May 14, 2011·Biochemistry·G BrienN Bonnefoy-Berard
Jun 26, 2008·Journal of the American Chemical Society·Michael C McAlpineJames R Heath
Mar 20, 2001·Nature Reviews. Genetics·B R Stockwell
Aug 10, 2010·Acta Pharmacologica Sinica·Jing Li, Zhenping Zhu
Oct 8, 2005·Nature Biotechnology·H Kaspar BinzAndreas Plückthun
Mar 23, 2005·Nature Methods·Ian BurbulisRoger Brent
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·H ShiJ T Lis
Oct 16, 2001·Nucleic Acids Research·A H SimonsD Canaani
May 13, 2008·Protein Engineering, Design & Selection : PEDS·M DaiA R M Bradbury

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
B CohenR Brent
Proceedings of the National Academy of Sciences of the United States of America
M G Kolonin, R L Finley
Proceedings of the National Academy of Sciences of the United States of America
G CaponigroA Kamb
© 2021 Meta ULC. All rights reserved