Nanoparticles shed light on disease-causing proteins

Andy Tao uses a linear ion trap mass spectrometer to analyze several hundred proteins per hour. (Photo: Purdue Agricultural Communication/Tom Campbell)

Feb 13, 2007 — The problem with current protein profiling methods is that the small samples are so sensitive that “we can’t effectively use existing technologies to study them,” says Andy Tao, a Purdue University biochemist. In an effort to discover a better way to ascertain the presence, concentration, and function of proteins involved in disease processes, Tao and his colleagues bound a complex nanomolecule, called a dendrimer, with a glowing identification tag delivered to specific proteins in living venom cells from a rattlesnake.

The researchers hope the new method will also facilitate better, more efficient diagnosis in living cells and patients. Because molecular interactions and protein functions are disturbed when samples are collected, researchers can’t obtain an accurate picture of biochemical mechanisms related to illnesses such as cancer and heart disease.

Tao and his research team used dendrimers because they can pass through cell walls efficiently with little disturbance to the cells and then label specific proteins with isotopic tags while cells are still alive. This allows the scientists to determine the activities of proteins that play roles in specific diseases. Proteins carry genetic messages throughout the cell causing biochemical changes that can determine whether a cell behaves normally or abnormally. Proteins also are important in directing immune responses.

The team, which includes Purdue postdoctoral student Minjie Guo and Purdue graduate student Jacob Galan, report on their new strategy to discover proteins and protein levels, called soluble polymer-based isotopic labeling (SoPIL), in the current issue of the journal Chemical Communications. The study also is featured in the journal’s news publication Chemical Biology.

The dendrimers would carry one of the stable isotopic or fluorescent labels to identify the presence or absence of a protein that can be further developed for use as a disease indicator, or biomarker.

Snake venom cells were used because they have a very high concentration of proteins similar to some found in human blood, Tao said. The proteins apparently are part of the biochemical process that affects blood clotting or hemorrhage. Understanding how the proteins behave could help determine predisposition to heart disease and cancer and also be useful in diagnosis and drug development.

In future research, Tao plans to investigate how dendrimers are able to enter the cell so easily, what happens to them once they are in the cell and whether there are any long-term effects.

Purdue University and the National Institutes of Health’s National Heart, Lung and Blood Institute provided funding for this study.


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