Using a rare metal that's not utilized¹（利用） by nature, Rice University chemists have created a synthetic²（合成的） enzyme³ that could help unlock the identities of thousands of difficult-to-study proteins, including many that play key roles in cancer and other diseases. The research was published online this week in the Journal of the American Chemical Society.

"We have combined the chemical capabilities⁴ of rhodium（铑） with what biology already knows about recognizing and selecting specific proteins," said study co-author Zachary Ball, assistant professor of chemistry at Rice. "The result is a tool that, in many ways, is more powerful than any biological or chemical approach alone."

Ball began studying dirhodium catalysts⁶（催化剂） more than three years ago. He did not start out trying to create enzymes⁷ with them, but he was intrigued⁸（吸引，迷惑） by a study that showed dirhodium catalysts could be used to modify tryptophan（色氨酸） , one of the 21 amino acids（氨基酸） that are the basic building blocks of life.

Catalysts enhance chemical reactions by increasing the rate of reaction without being consumed（消耗） themselves. In living things, proteins called enzymes serve the same purpose. But unlike many inorganic⁹ catalysts, enzymes are very selective. In a process that biologists often liken to a "lock and key," enzymes associate only with molecules¹⁰ that match their shape exactly. This prevents them from spurring（激励，鞭策） extraneous¹¹（外来的） reactions throughout the cell.

Ball and postdoctoral research associate Brian Popp wondered if they could marry the selectivity of enzymatic¹² reactions with a rhodium-based catalyst⁵. They tested the idea by attaching their catalyst to a short segment of protein that can wrap with other proteins, like strands¹³ of rope fiber¹⁴. This "coiled coil" wrapping motif¹⁵（主题，动机） is common in biology, particularly in signaling proteins. Signaling proteins are those that activate¹⁶ or deactivate¹⁷ key processes like apoptosis（细胞死亡） , the "programmed death" response that's known to play a key role in cancer.

"Signaling pathways are like a trail of dominos（多米诺骨牌） ," Ball said. "Dozens of proteins can be involved, and they interact one after the other in a cascade¹⁸（小瀑布，喷流） . In most cases, the interactions are both fleeting¹⁹ and weak. They are difficult to observe with traditional methods, and as a result we are still in the dark about the roles that key signaling proteins play in health and disease."

Ball said his and Popp's synthetic enzyme strategy might help solve that problem. In their tests, the chemists were able to develop synthetic enzymes that could selectively bind²⁰ with proteins and attach tags that would allow biologists to identify them.

In addition to tryptophan, the method worked with phenylalanine（苯基丙氨酸） and tyrosine（酪氨酸） , two amino acids commonly found in signaling proteins. And recent unpublished studies indicate the researchers' strategy might work for even more amino acids.

Ball said the process must be refined before it can be used in the majority of biology labs, but he and Popp are already working toward realizing broad applications of the strategy.