Inhibition of chymotrypsin through surface binding using nanoparticle-based receptors

Proceedings of the National Academy of Sciences of the United States of America
Nicholas O FischerVincent M Rotello

Abstract

Efficient binding of biomacromolecular surfaces by synthetic systems requires the effective presentation of complementary elements over large surface areas. We demonstrate here the use of mixed monolayer protected gold clusters (MMPCs) as scaffolds for the binding and inhibition of chymotrypsin. In these studies anionically functionalized amphiphilic MMPCs were shown to inhibit chymotrypsin through a two-stage mechanism featuring fast reversible inhibition followed by a slower irreversible process. This interaction is very efficient, with a K(i)(app) = 10.4 +/- 1.3 nM. The MMPC-protein complex was characterized by CD, demonstrating an almost complete denaturation of the enzyme over time. Dynamic light scattering studies confirm that inhibition proceeds without substantial MMPC aggregation. The electrostatic nature of the engineered interactions provides a level of selectivity: little or no inhibition of function was observed with elastase, beta-galactosidase, or cellular retinoic acid binding protein.

References

Nov 1, 1979·Analytical Biochemistry·E G DelMarM C Geokas
Jul 1, 1991·European Journal of Biochemistry·R Bru, P Walde
Jan 25, 1973·Biochimica Et Biophysica Acta·R J Siezen, R van Driel
Aug 15, 1996·Nature·A P AlivisatosP G Schultz
Jan 1, 1996·Annual Review of Biophysics and Biomolecular Structure·M Mrksich, G M Whitesides
Jul 17, 1998·Current Opinion in Chemical Biology·R ZutshiJ Chmielewski
Aug 26, 1998·Chemistry & Biology·I Ghosh, J Chmielewski
Feb 23, 1999·Biochemistry·K NadassyJ Janin
Jun 29, 1999·Biological Chemistry·H J SchrammW Schramm
Aug 2, 2001·Journal of the American Chemical Society·C M McIntoshV M Rotello
Dec 26, 2001·Chemical Reviews·M W Peczuh, A D Hamilton
Jan 17, 2002·Bioconjugate Chemistry·Kulmeet K SandhuVincent M Rotello

❮ Previous
Next ❯

Citations

Nov 26, 2010·Pharmaceutical Research·Sanjib BhattacharyyaPriyabrata Mukherjee
Nov 2, 2013·Journal of Inorganic Biochemistry·Jasmina C Cheung-LauIvan J Dmochowski
Jan 9, 2013·Accounts of Chemical Research·Sung Tae KimVincent M Rotello
Oct 1, 2011·Journal of the American Chemical Society·Mrinmoy DeVinayak P Dravid
Jun 24, 2008·Journal of the American Chemical Society·Maksym V YezhelyevXiaohu Gao
May 4, 2011·The Journal of Organic Chemistry·Ilaria D'AcquaricaBruno Botta
Apr 12, 2011·Langmuir : the ACS Journal of Surfaces and Colloids·Daniel F Moyano, Vincent M Rotello
Jun 4, 2011·Langmuir : the ACS Journal of Surfaces and Colloids·Jia-Qi LinZhen Chen
Jul 26, 2008·Nature Nanotechnology·Chang-Cheng YouVincent M Rotello
Aug 3, 2005·Chemical Communications : Chem Comm·Tai Hwan HaBong Hyun Chung
May 31, 2006·Chemical Communications : Chem Comm·Joseph W E WorrallVincent M Rotello
Jul 20, 2006·Journal of the Royal Society, Interface·Steven Fletcher, Andrew D Hamilton
Jan 9, 2010·International Journal of Molecular Sciences·Zhaochun WuBing Yan
Mar 19, 2014·Langmuir : the ACS Journal of Surfaces and Colloids·Takaaki KurinomaruKentaro Shiraki
Jul 28, 2005·Journal of the American Chemical Society·Britto S SandanarajS Thayumanavan
Apr 23, 2010·Expert Opinion on Drug Delivery·Rochelle ArvizoPriyabrata Mukherjee
Jan 30, 2016·Trends in Biotechnology·Youhui LinXiang Yang Liu
Oct 10, 2015·Science·Carlos A Silvera BatistaNicholas A Kotov
Dec 17, 2009·Journal of Controlled Release : Official Journal of the Controlled Release Society·Dakrong PissuwanMichael B Cortie
Sep 23, 2008·Trends in Biotechnology·Jungbae KimPing Wang
Oct 26, 2005·Current Opinion in Chemical Biology·Steven Fletcher, Andrew D Hamilton
Oct 18, 2005·Current Opinion in Chemical Biology·Chang-Cheng YouVincent M Rotello
Apr 13, 2005·Otolaryngologic Clinics of North America·G Louis Hornyak
Jan 29, 2016·Journal of Biomolecular Structure & Dynamics·Jessy MariamP M Dongre
Jun 21, 2015·Journal of Photochemistry and Photobiology. B, Biology·Nahid ShahabadiLeila Nemati
Oct 6, 2016·Nanotoxicology·Géraldine KleinJean Labarre
Jan 14, 2017·Biomacromolecules·Chad S CummingsAlan J Russell
Jan 6, 2007·Organic & Biomolecular Chemistry·Andrew J WilsonAndrew D Hamilton
Nov 1, 2007·Chemistry : a European Journal·Chang-Cheng YouVincent M Rotello
Jul 1, 2006·Chembiochem : a European Journal of Chemical Biology·Raphaël Lévy
Apr 19, 2007·Chemistry, an Asian Journal·Markus ArendtThomas Schrader
Mar 4, 2008·Chemistry, an Asian Journal·Koji Kano, Yoshiyuki Ishida
Jun 15, 2005·Angewandte Chemie·Hang Yin, Andrew D Hamilton

❮ 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.

© 2022 Meta ULC. All rights reserved