Heterogeneous-Backbone Foldamer Mimics of Zinc Finger Tertiary Structure

Journal of the American Chemical Society
Kelly L George, W Seth Horne

Abstract

A variety of oligomeric backbones with compositions deviating from biomacromolecules can fold in defined ways. Termed "foldamers," these agents have diverse potential applications. A number of protein-inspired secondary structures (e.g., helices, sheets) have been produced from unnatural backbones, yet examples of tertiary folds combining several secondary structural elements in a single entity are rare. One promising strategy to address this challenge is the systematic backbone alteration of natural protein sequences, through which a subset of the native side chains is displayed on an unnatural building block to generate a heterogeneous backbone. A drawback to this approach is that substitution at more than one or two sites often comes at a significant energetic cost to fold stability. Here we report heterogeneous-backbone foldamers that mimic the zinc finger domain, a ubiquitous and biologically important metal-binding tertiary motif, and do so with a folded stability that is superior to the natural protein on which their design is based. A combination of UV-vis spectroscopy, isothermal titration calorimetry, and multidimensional NMR reveals that suitably designed oligomers with >20% modified backbones can form native-like te...Continue Reading

References

Aug 8, 1978·Biochemistry·S W May, J Y Kuo
Jun 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·S F MichaelJ M Berg
Nov 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·D P GiedrocJ E Coleman
Nov 10, 1981·Biochemistry·M VasákB L Vallee
Dec 1, 1994·Protein Science : a Publication of the Protein Society·E G Hutchinson, J M Thornton
Jan 1, 1997·Annual Review of Biophysics and Biomolecular Structure·J M Berg, H A Godwin
May 29, 1998·Biochimica Et Biophysica Acta·T MiuraH Takeuchi
Jun 27, 1998·Journal of Molecular Biology·J H VilesJ M Thornton
Apr 15, 2000·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·X ChenD P Giedroc
Sep 26, 2002·Journal of the American Chemical Society·Richard P Cheng, William F DeGrado
Nov 5, 2002·Nature Medicine·Edward J RebarFrank J Giordano
Jan 23, 2003·Journal of the American Chemical Society·James S Nowick, Justin O Brower
Feb 8, 2003·Proceedings of the National Academy of Sciences of the United States of America·Lindsey ReynoldsYen Choo
Jul 28, 2005·Journal of the American Chemical Society·Fan ZhangJoseph M Fox
Dec 20, 2005·Chemical Research in Toxicology·Jason L LarabeeJay S Hanas
Aug 3, 2006·Journal of the American Chemical Society·Yan Zhao, Zhenqi Zhong
Aug 31, 2006·Journal of the American Chemical Society·Jade X QiuAlanna Schepartz
Oct 20, 2006·Angewandte Chemie·Nicolas DelsucIvan Huc
Mar 17, 2007·Journal of the American Chemical Society·W Seth HorneSamuel H Gellman
Apr 18, 2007·Nature Chemical Biology·Catherine M GoodmanWilliam F DeGrado
Nov 9, 2007·Current Opinion in Chemical Biology·Arjel D BautistaAlanna Schepartz
Jun 3, 2008·Chemistry : a European Journal·Christian E SchafmeisterPatrick H Brown
Jun 27, 2008·Accounts of Chemical Research·Dieter Seebach, James Gardiner
Jul 4, 2008·Journal of the American Chemical Society·Byoung-Chul LeeRonald N Zuckermann
Apr 24, 2009·Chemistry : a European Journal·Olivier SénèqueJean-Marc Latour
Feb 11, 2011·Journal of the American Chemical Society·Nicolas DelsucIvan Huc
Apr 13, 2011·Chemical Communications : Chem Comm·Gilles Guichard, Ivan Huc
Jun 4, 2011·Inorganic Chemistry·Zhijie MaCatalina Achim
Jul 20, 2011·Chemical Society Reviews·Tamás A Martinek, Ferenc Fülöp
May 18, 2012·Journal of the American Chemical Society·Anne M RichDean E Wilcox
Nov 17, 2012·Angewandte Chemie·Shohei TashiroMitsuhiko Shionoya
Apr 4, 2013·Journal of the American Chemical Society·Pin-Nan ChengJames S Nowick
Aug 14, 2013·Journal of the American Chemical Society·Zachary E ReinertW Seth Horne
Oct 4, 2013·Journal of the American Chemical Society·Zsófia HegedüsTamás A Martinek
Jun 1, 2014·Accounts of Chemical Research·Charles A GersbachCarlos F Barbas
Jun 10, 2014·Organic & Biomolecular Chemistry·George A LengyelW Seth Horne
Jun 16, 2014·Nature Biotechnology·Ross W ChelohaSamuel H Gellman
Jun 18, 2014·ACS Chemical Biology·Thomas GajCarlos F Barbas
Jul 30, 2014·Chemical Science·Zachary E Reinert, W Seth Horne
Aug 12, 2014·Metallomics : Integrated Biometal Science·Anna Miłoch, Artur Krężel
Oct 8, 2014·Journal of the American Chemical Society·Jonathan P MillerAlanna Schepartz

❮ Previous
Next ❯

Citations

Dec 23, 2017·Chembiochem : a European Journal of Chemical Biology·David E MortensonKatrina T Forest
Oct 17, 2018·Chembiochem : a European Journal of Chemical Biology·Chino C CabaltejaW Seth Horne
Feb 6, 2019·Chemical Communications : Chem Comm·Imane NekkaaIstván M Mándity
Dec 19, 2017·Chembiochem : a European Journal of Chemical Biology·Kathrin Lang
Feb 16, 2020·Angewandte Chemie·Min ZhouRunhui Liu
May 7, 2019·Chembiochem : a European Journal of Chemical Biology·Halina M WernerW Seth Horne
Feb 8, 2020·Nature Chemistry·W Seth Horne, Tom N Grossmann
Jan 9, 2021·ChemPlusChem·Shilpa R RaoW Seth Horne
Feb 27, 2020·Chemical Reviews·Moran Frenkel-PinterLuke J Leman
Mar 19, 2021·Peptide Science·Shilpa R Rao, W Seth Horne
May 12, 2021·Journal of Molecular Recognition : JMR·Robert J FalconerAnthony K Mittermaier
May 20, 2021·Organic & Biomolecular Chemistry·Magda Drewniak-SwitalskaŁukasz Berlicki
Jun 8, 2021·Chemical Science·Attila TököliTamás A Martinek
Apr 20, 2018·Accounts of Chemical Research·Kelly L George, W Seth Horne
Feb 5, 2019·Journal of the American Chemical Society·Caterina Maria LombardoGilles Guichard

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.