ORGANIC
LETTERS
2007
Vol. 9, No. 12
2381-2383
Introduction of a Triazole Amino Acid
into a Peptoid Oligomer Induces Turn
Formation in Aqueous Solution
Jonathan K. Pokorski,§ Lisa M. Miller Jenkins,† Hanqiao Feng,‡
Stewart R. Durell,† Yawen Bai,‡ and Daniel H. Appella*,§
Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, DHHS,
Bethesda, Maryland 20892, Laboratory of Cell Biology, NCI, National Institutes
of Health, DHHS, Bethesda, Maryland 20892, and Laboratory of Biochemistry
and Molecular Biology, NCI, National Institutes of Health, DHHS,
Bethesdsa Maryland 20892.
Received April 5, 2007
ABSTRACT
Peptoids are a non-natural class of oligomers that are composed of repeating N-substituted glycine units and are capable of folding into
helices that mimic peptide structure and function. In this letter, we report the concise synthesis of a 1,5-substituted triazole amino acid (Tzl)
and its subsequent incorporation into a short peptoid. The Tzl amino acid was shown to induce turn formation in aqueous solution, thus
expanding the structural repertoire available to peptoid chemists.
Peptoids are a class of synthetic oligomers that consist of
repeating N-substituted glycine units and are capable of
folding into discrete structures.1 Peptoids bearing R-branched
side chains can fold into helices resembling the polyproline
type I (PPI) helix2 and are attractive pharmaceutical candi-
dates because of their enhanced proteolytic stability3 and
cellular uptake.4 In this context, peptoids’ propensity for helix
formation has been used to develop mimics of the antibacte-
rial magainin peptides5 and lung surfactant proteins.6 More
recently, macrocyclic peptoids were designed to mimic â-turn
formation in organic solvents.7 Expanding the structural
repertoire of peptoids to include turns, loops, and sheets
should aid the development of biologically active derivatives
where such motifs are relevant. Progress in the development
of noncyclic peptoid structure has shown that certain
nonamers can fold into loops in organic solvent,8 which can
be stabilized through the introduction of electron-poor
§ Laboratory of Bioorganic Chemistry.
† Laboratory of Cell Biology.
‡ Laboratory of Biochemistry and Molecular Biology.
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10.1021/ol070817y This article not subject to U.S. Copyright. Published 2007 by the American Chemical Society
Published on Web 05/17/2007