Engineered chemical trap detects rare glycoproteins emitted as cancer first develops.
Researchers at the Georgia Institute of Technology have designed a boronic acid derivative that can bind to rare glycoproteins produced during the earliest stages of cancer.
Glycoproteins – or proteins bonded with sugar molecules – are common in the body and play critical roles in many biological functions, particularly via the formation of cellular structures such as cell receptors. Glycoproteins can also be produced in trace quantities at the onset of disease. If these glycoproteins could be detected, they could serve as important biomarkers and enable early detection and treatment.
"These tiny traces are critically important for early disease detection," said principal investigator Ronghu Wu, a professor in Georgia Tech's School of Chemistry and Biochemistry. "When cancer is just getting started, aberrant glycoproteins are produced and secreted into body fluids such as blood and urine. Often their abundances are extremely low, but catching them is urgent."
Developing such a diagnostic tool has been a real challenge, though. The scientists at Georgia Tech took years to identify an effective “chemical trap.” The boronic acid derivative has proven effective in lab tests including on cultured human cells and mouse tissue samples. It is able to detect over 1000 glycoproteins in a small sample – exponentially more, and particularly more of the important trace molecules – than existing methods.
The boronic acid derivative comprises a dendrimer of benzoboroxole units and other building blocks that together form a highly branched structure that resembles an octopus. A magnetic bead is located at the center of the structure to enable retrieval of the molecule and any bound glycoproteins. The glycoproteins are released from the dendrimer by washing with a low-pH solution and then analyzed using mass spectrometry.
The researchers believe their new diagnostic tool could be used to detect prostate-specific antigens (PSA) as a screen for prostate cancer. "PSA is a glycoprotein. Right now, if the level is very high, we know that the patient may have cancer, and if it's very low, we know cancer is not likely," Wu said. "But there is a gray area in between, and this method could lead to much more detailed information in that gray area."
They also believe there is potential to use the trace glycoproteins as cancer immunotherapy targets.