Annie Tam, U. Arnold, M. Soellner
Oct 24, 2007
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Influential Citations
187
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Journal
Journal of the American Chemical Society
Abstract
Proline is unique among the natural amino acids in the similar propensity of its peptide bond to be in the cis or trans conformation. This attribute affects many processes, including the rate at which proteins fold, their structures, and their activities. Other aliphatic amino acids can serve as mimics for proline residues with trans-peptide bonds. In contrast, chemical synthesis is needed to create surrogates for cis-prolyl peptide bonds. Here, 1,5-disubstituted[1,2,3]triazoles were assessed as cis-peptide bond surrogates. Huisgen's 1,3-dipolar cycloaddition reaction of amino alkynes and azido acids and a Ru(II) catalyst was used to synthesize a variety of Xaa-1,5-triazole-Ala modules in moderate-to-high yields. Two of these modules, along with their 1,4-triazole regioisomers, were installed in a turn region of bovine pancreatic ribonuclease by using expressed protein ligation. The resulting semisynthetic enzymes displayed full enzymatic activity, indicating the maintenance of native structure. The 1,5-t...