化学家成功运用缩氨酸模拟酶类活动

Chemists in The College of Arts and Sciences have, for the first time, created enzyme ¹-like activity using peptides（缩氨酸） that are only seven amino acids long. A rendering ² of a catalytic amyloid-forming peptide, with zinc ³ ions shown as gray spheres., ,Their breakthrough, which is the subject of a recent article in Nature Chemistry magazine (Macmillan Publishers, 2014), may revolutionize the study of modern-day enzymes ⁴, whose chains of amino acids usually number in the hundreds, and of neurological diseases, such as Alzheimer's, which are usually characterized by small clumps ⁶ of misshapen（畸形的） proteins called amyloids（淀粉体）., ,Their finding also supports the theory that amyloid fibrils -- strong, highly organized fibers ⁷, formed by proteins and peptides -- may have predated enzymes and triggered reactions that led to some of the earliest forms of life., ,"Enzymes fold into unique three-dimensional structures, which underlie ⁸ their remarkable ⁹ catalytic properties and contribute to their large size," says Ivan V. Korendovych, assistant professor of chemistry, who co-led the study with William DeGrado, SU professor of pharmaceutical ¹⁰ chemistry at the University of California, San Francisco (UCSF). "Our goal was to prove that much shorter peptides can also achieve well-defined conformations through the formation of amyloid fibrils.", ,Korendovych and his team designed seven simple peptides, each containing seven amino acids. They then allowed the molecules ¹² of each peptide to self-assemble, or spontaneously clump ⁵ together, to form amyloids. (Zinc, a metal with catalytic properties, was introduced to speed up the reaction.) What they found was that four of the seven peptides catalyzed ¹⁴ the hydrolysis of molecules known as esters（酯类）, compounds that react with water to produce water and acids -- a feat ¹⁵ not uncommon ¹⁶ among certain enzymes., ,"It was the first time that a peptide this small self-assembled to produce an enzyme-like catalyst," says Korendovych, an expert in bioinorganic chemistry, biophysics and chemical biology. "Our finding suggests that amyloids, whose buildup leads to Alzheimer's in the brain, may also have served as the blueprint ¹⁷ for larger, modern-day enzymes.", ,That's good news for researchers such as Korendovych, who thinks this finding may lead to the development of a new class of synthetic ¹⁸ peptide-based catalysts ¹⁹. "The amyloid structures we've created may have a more complex biochemistry than we've realized," he says., ,There are 20 naturally occurring amino acids, all of which serve as the building blocks of proteins and assist with metabolism ²⁰., ,An enzyme is a type of protein that is composed of at least 100 amino acids and speeds up reactions in a cell., ,Korendovych says that, despite an astronomically ²¹ large number of possible enzymes (each with a different amino acid sequence and three-dimensional shape), only a small number of them actually work., ,"Each enzyme has to be an exact fit for its respective substrate," he says, referring to the molecule ¹¹ with which an enzyme reacts. "Even after millions of years, nature is still testing all the possible combinations of enzymes to determine which ones can catalyze ¹³ metabolic ²² reactions. Our results make an argument for the design of self-assembling nanostructured catalysts."