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Serum Peptide Profile May Be New Dx Biomarker

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Researchers at the Memorial Sloan-Kettering Cancer Center have found that the degradation products of relatively high-abundance blood proteins, which had previously been dismissed by some as waste products that serve no diagnostic purpose, may actually serve as good biomarkers for disease.

The marker peptides may be formed when proteases specific for disease cleave the relatively abundant blood proteins, which serve as substrates, explains Paul Tempst, the leader of a study published in the Journal of Clinical Investigation.

While the disease-specific proteases themselves are not abundant enough in blood to be seen by regular proteomics experiments, the serum peptidome, which contains disease-specific cleavage fragments of known proteins and peptides, could serve as a new type of biomarker, Tempst says.

“Basically, we were lucky to pick up this activity,” Tempst says. “There are a lot of low-concentration enzymes you can’t see, but if you give them enough time and enough substrate, you can get a catalytic product that’s measurable with MALDI-TOF.”

Lance Liotta and Emanuel Petricoin wrote in a commentary that accompanied the paper that while some researchers have dismissed the serum peptidome as “biological trash,” Tempst’s work shows that the peptidome may, in fact, contain “diagnostic gold.”

“The implications for the diagnostics arena are enormous,” wrote Liotta and Petricoin, both researchers at George Mason University. “Fingerprints of MS ions can be replaced with panels of named protein biomarkers.”

Benjamin Cravatt, a proponent of “activity-

based proteomics” at the Scripps Research Institute, concurs. “This work is highly significant because it provides evidence that different tumor types secrete and/or shed distinct sets of proteases that, through their catalytic activity, generate unique serum peptide profiles,” according to Cravatt. “These peptide profiles can in turn be used as patterns to accurately predict the presence of a particular tumor type in patients.”                      
— Tien-Shun Lee

PATENT WATCH
US Patent 6,989,531. Mass spectrometer. Inventors: Atsumu Hirabayashi, Masako Ishimaru, and Masahiro Yamaoka. Assignee: Hitachi. Issued: January 24, 2006.

This patent protects an invention relating to “an LC/MS interface provided with structure that the end of a spray capillary is rarely damaged and the object is to provide the LC/MS interface which a general user can easily operate, which inhibits the extension of a separation band and the deterioration of detection sensitivity, and which enables high separation and sensitive analysis,” according to the abstract.


US Patent 6,989,530. Ambient pressure matrix-assisted laser desorption ionization (MALDI) apparatus and method of analysis. Inventors: Jian Bai, Steven Fischer, and Michael Flanagan. Assignee: Agilent Technologies. Issued: January 24, 2006.

This patent deals with “a mass spectrometer having a matrix-assisted laser desorption ionization (MALDI) source which operates at ambient pressure” as well as with methods to operate the instrument, according to the abstract.


Caprion Pharmaceuticals and Icos will collaborate to identify pharmacodynamic markers in plasma using Caprion’s proteomics platform. Icos plans to use the research in its preclinical oncology programs.

Manipal AcuNova, a Bangalore-based joint venture between Manipal Education and Medical Group and AcuNova, has deployed Thermo Electron’s Finnegan TSQ Quantum Ultra mass spectrometer. Manipal plans to use the triple quadrupole mass spec in high-throughput drug metabolism and pharmacokinetics lab work.

Vitro Diagnostics and PhosphoSolutions have teamed up to work on stem cell proteomics research in which the companies will investigate intracellular signaling mechanisms involved with regulation of stem cell growth and differentiation.

ActiveSight, a division of Rigaku that features a portfolio of drug targets for co-crystallography, will provide protein crystallography services to Novo Nordisk.

A year after acquiring Incyte’s Proteome database unit, Biobase launched ExPlain, a pathway analysis software package.

Researchers from St. Jude Children’s Research Hospital completed a broad analysis on the genome sequences of different virus strains and found a unique protein that appears to be responsible for the high mortality of the ongoing H5N1 bird flu outbreak in Asia and Europe.

Datapoint
2 percent
Waters reported that sales of mass specs increased 2 percent in the fourth quarter of 2005, as compared to the same quarter the year before. Sales of Q-TOFs, on the other hand, grew more than 20 percent during 2005.

 

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