Merck + Co., Inc.

Other

Battelle Memorial Institute

University of Washington

James E Bruce

Richard Dale Smith

Stephen F Brady

Victor M Garsky

Jules A Shafer

Yueming Li

Mohinder Sardana

Elizabeth Chen-Dodson

Xiaoting Tang

Gordon A Anderson

David R Goodlett

Beate Rist

Ruedi Aebersold

Ljiljana Pasa-Tolic

Chad Weisbrod

Juan Chavez

Michael D Brands

Disclosed herein are methods for large-scale, high-throughput identification of protein-protein interactions and the topologies thereof under physiologically relevant conditions. In one aspect, the disclosure provides methods for identifying one or a plurality of interacting peptides within a biological system comprising obtaining a population of proteins cross-linked with a cleavable protein interaction reporter (PIR) cross-linker, cleaving the PIR crosslinker to produce released peptides and cleaved reporter ions, and analyzing the population of released peptides to identify interacting peptides. Also disclosed are methods for identifying candidate drug compounds, as well as methods of data processing and visualization of protein-protein interactions.

Real-time analysis for cross-linked peptides

The present invention provides synthetic &#x3b2;-secretase peptide substrates useful in various assays for measuring &#x3b2;-secretase activity. Antibodies that recognize the synthetic substrates and uses of the antibodies in various assays are disclosed. The herein disclosed peptide substrates are hydrolyzed at rates substantially faster than the attendant Swedish mutant APP from which the substrate sequences are derived.

Beta-secretase substrates and uses thereof

The present invention provides methods and reagents for identifying specific masses of compounds in a complex mixture. In particular, the present invention describes an isotope distribution encoded tag (IDEnT) concept wherein the ability to distinguish an analyte encoded with a non-native isotope from those not encoded with the isotope or from those encoded with a different isotope is used for protein identification, enzyme active site identification, peptide sequencing, and the like. Reagents used in the IDEnT strategy consist of a chemical element with a unique isotope distribution not normally found in the analyte class being studied, chemically bonded to, or an integral part of a chemical reagent with a high selectivity of affinity for specific functional group in the analyte.

Isotope distribution encoded tags for protein identification

A method whereby a mass spectra generated by a mass spectrometer is calibrated by shifting the parameters used by the spectrometer to assign masses to the spectra in a manner which reconciles the signal of ions within the spectra having equal mass but differing charge states, or by reconciling ions having known differences in mass to relative values consistent with those known differences. In this manner, the mass spectrometer is calibrated without the need for standards while allowing the generation of a highly accurate mass spectra by the instrument.

Method for calibrating mass spectrometers

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Schwenksville, PA, United States of America

James E Bruce