Chemists in Syracuse University's College of Arts and Sciences have, for the first time, created enzyme-like activity using peptides that are only seven amino acids long.
Their breakthrough, which is the subject a recent article in Nature Chemistry magazine (Macmillan Publishers, 2014), may revolutionize the study of modern-day enzymes, 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 of misshaped proteins called amyloids.
Their finding also supports the theory that amyloid fibrilsstrong, highly organized fibers, formed by proteins and peptidesmay 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 their remarkable catalytic properties and contribute to their large size," says Ivan V. Korendovych, assistant professor of chemistry at SU, who co-led the study with William DeGrado, professor of pharmaceutical 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 of each peptide to self-assemble, or spontaneously clump 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 the hydrolysis of molecules known as esters, compounds that react with water to produce water and acidsa feat not uncommon 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 find
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