Journal ArticleDOI
Screening derivatized peptide libraries for tight binding inhibitors to carbonic anhydrase II by electrospray ionization-mass spectrometry.
Jinming Gao,Xueheng Cheng,Ruidan Chen,George Sigal,James E. Bruce,Brenda L. Schwartz,Steven A. Hofstadler,Gordon A. Anderson,Richard D. Smith,George M. Whitesides +9 more
TLDR
The ability of ESI-MS to estimate simultaneously the relative binding affinities of a protein to soluble ligands in a library, if general, should be useful in drug development.Abstract:
This paper describes the use of electrospray ionization-mass spectrometry (ESI-MS) to screen two libraries of soluble compounds to search for tight binding inhibitors for carbonic anhydrase II (EC 4.2.1.1). The two libraries, H2NO2SC6H4C(O)NH-AA1-AA2-C(O)NHCH2CH2CO2H (1), where AA1 and AA2 are l-amino acids (library size: 289 compounds) or d-amino acids (256 compounds), were constructed by attaching tripeptides to the carboxyl group of 4-carboxybenzenesulfonamide. Screening of both libraries yielded, as the tightest binding inhibitor, compound 1 (AA1 = AA2 = l-Leu; binding constant Kb = 1.4 × 108 M-1). The ability of ESI-MS to estimate simultaneously the relative binding affinities of a protein to soluble ligands in a library, if general, should be useful in drug development.read more
Citations
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PatentDOI
Carbonic anhydrase inhibitors
Peter Ebbesen,Claudlu T. Supuran,Andrea Scozzafava,Erik Olai Pettersen,Kaye Williams,L.J. Dubois,Philippe Lambin +6 more
TL;DR: A carbonic anhydrase IX (CA IX) inhibitor is a compound of general formula: R-NH-CX-NH-(CH 2 ) n -Ar-Q-SO 2 -NH 2 or a pharmaceutically acceptable salt, derivative or prodrug thereof.
Journal ArticleDOI
Studying noncovalent protein complexes by electrospray ionization mass spectrometry
TL;DR: Several applications of ESI-MS are discussed, including protein interactions with metal ions and nucleic acids and subunit protein structures (quaternary structure) and mass spectrometry offers advantages in speed and sensitivity.
Journal ArticleDOI
Multiple Binding Modes of Inhibitors to Carbonic Anhydrases: How to Design Specific Drugs Targeting 15 Different Isoforms?
Journal ArticleDOI
Carbonic Anhydrase as a Model for Biophysical and Physical-Organic Studies of Proteins and Protein–Ligand Binding
Vijay M. Krishnamurthy,George K. Kaufman,Adam R. Urbach,Irina Gitlin,Katherine L. Gudiksen,Douglas B. Weibel,George M. Whitesides +6 more
TL;DR: Carbonic anhydrase is a protein that is especially well-suited to serve as a model in many types of studies in biophysics, bioanalysis, the physical-organic chemistry of inhibitor design, and medicinal chemistry.
Journal ArticleDOI
Quantitative determination of noncovalent binding interactions using soft ionization mass spectrometry
TL;DR: In this paper, the results of these studies, as well as the methods employed are reviewed, and the possibility to quantitatively measure solution-phase and gas-phase non-covalent interaction strengths by mass spectrometry opens fascinating perspectives for very high sensitivity screening assays as well and for improved fundamental understanding of the nature of non covalent interactions.
References
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Journal ArticleDOI
Electrospray ionization for mass spectrometry of large biomolecules
TL;DR: Spectra have been obtained for biopolymers including oligonucleotides and proteins, the latter having molecular weights up to 130,000, with as yet no evidence of an upper limit.
Journal ArticleDOI
A new type of synthetic peptide library for identifying ligand-binding activity
Kit S. Lam,Sydney E. Salmon,Evan M. Hersh,Victor J. Hruby,Wieslaw M. Kazmierski,Richard J. Knapp +5 more
TL;DR: The simple methodology greatly enhances the production and rapid evaluation of random libraries of millions of peptides so that acceptor-binding ligands of high affinity can be rapidly identified and sequenced, on the basis of a "one-bead, one-peptide9 approach.
Journal ArticleDOI
Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery
Richard A. Houghten,Clemencia Pinilla,Sylvie E. Blondelle,Jon R. Appel,Colette T. Dooley,Julio H. Cuervo +5 more
TL;DR: The precise identification of an antigenic determinant recognized by a monoclonal antibody as well as the straightforward development of new potent antimicrobial peptides are presented.
Journal ArticleDOI
New developments in biochemical mass spectrometry: electrospray ionization
TL;DR: Fundamental considerations suggest even more impressive developments may be anticipated related to detection sensitivity and methods for obtaining structural information, as well as new developments related to ESI-MS.
Journal ArticleDOI
Some developments in nuclear magnetic resonance of solids.
TL;DR: Nuclear magnetic resonance (NMR) spectroscopy continues to evolve as a primary technique in the study of solids as discussed by the authors, enabling increasingly complex structural and dynamical behavior to be probed at a molecular level and thus add to our understanding of macroscopic properties of materials.