Increasing the Functional Group Diversity in Helical beta-Peptoids: Achievement of Solvent- and pH-Dependent Folding
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Increasing the Functional Group Diversity in Helical beta-Peptoids : Achievement of Solvent- and pH-Dependent Folding. / Wellhofer, Isabelle; Beck, Janina; Frydenvang, Karla; Brase, Stefan; Olsen, Christian A.
In: Journal of Organic Chemistry, Vol. 85, No. 16, 2020, p. 10466-10478.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Increasing the Functional Group Diversity in Helical beta-Peptoids
T2 - Achievement of Solvent- and pH-Dependent Folding
AU - Wellhofer, Isabelle
AU - Beck, Janina
AU - Frydenvang, Karla
AU - Brase, Stefan
AU - Olsen, Christian A.
PY - 2020
Y1 - 2020
N2 - We report the synthesis of a series of bis-functionalized beta-peptoid oligomers of the hexamer length. This was achieved by synthesizing and incorporating protected amino- or azido-functionalized chiral building blocks into precursor oligomers by a trimer segment coupling strategy. The resulting hexamers were readily elaborated to provide target compounds displaying amino groups, carboxy groups, hydroxy groups, or triazolo-pyridines, which should enable metal ion binding. Analysis of the novel hexamers by circular dichroism (CD) spectroscopy and H-1-C-13 heteronuclear single quantum coherence nuclear magnetic resonance (HSQC NMR) spectroscopy revealed robust helical folding propensity in acetonitrile. CD analysis showed a solvent-dependent degree of helical content in the structural ensembles when adding different ratios of protic solvents including an aqueous buffer. These studies were enabled by a substantial increase in solubility compared to previously analyzed beta-peptoid oligomers. This also allowed for the investigation of the effect of pH on the folding propensity of the amino- and carboxy-functionalized oligomers, respectively. Interestingly, we could show a reversible effect of sequentially adding acid and base, resulting in a switching between compositions of folded ensembles with varying helical content. We envision that the present discoveries can form the basis for the development of functional peptidomimetic materials responsive to external stimuli.
AB - We report the synthesis of a series of bis-functionalized beta-peptoid oligomers of the hexamer length. This was achieved by synthesizing and incorporating protected amino- or azido-functionalized chiral building blocks into precursor oligomers by a trimer segment coupling strategy. The resulting hexamers were readily elaborated to provide target compounds displaying amino groups, carboxy groups, hydroxy groups, or triazolo-pyridines, which should enable metal ion binding. Analysis of the novel hexamers by circular dichroism (CD) spectroscopy and H-1-C-13 heteronuclear single quantum coherence nuclear magnetic resonance (HSQC NMR) spectroscopy revealed robust helical folding propensity in acetonitrile. CD analysis showed a solvent-dependent degree of helical content in the structural ensembles when adding different ratios of protic solvents including an aqueous buffer. These studies were enabled by a substantial increase in solubility compared to previously analyzed beta-peptoid oligomers. This also allowed for the investigation of the effect of pH on the folding propensity of the amino- and carboxy-functionalized oligomers, respectively. Interestingly, we could show a reversible effect of sequentially adding acid and base, resulting in a switching between compositions of folded ensembles with varying helical content. We envision that the present discoveries can form the basis for the development of functional peptidomimetic materials responsive to external stimuli.
KW - SOLID-PHASE SYNTHESIS
KW - ASYMMETRIC-SYNTHESIS
KW - CHIRAL AMINES
KW - SIDE-CHAIN
KW - CIRCULAR-DICHROISM
KW - FOLDAMERS
KW - PEPTIDE
KW - BACKBONE
KW - SUBSTITUENTS
KW - STABILITY
U2 - 10.1021/acs.joc.0c00780
DO - 10.1021/acs.joc.0c00780
M3 - Journal article
C2 - 32806085
VL - 85
SP - 10466
EP - 10478
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
SN - 0022-3263
IS - 16
ER -
ID: 249301145