Journal of the American Chemical Society
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found to adopt essentially 100% -helical conformations
Figure 4, Figure S6). These results show that although it is
highly likely there is sulfoxide stereochemical disorder in
(4) (a) Lu, H.; Wang, J.; Bai, Y.; Lang, J. W.; Liu, S.; Lin, Y.;
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Cheng, J. Ionic polypeptides with unusual helical stability. Nat.
Commun. 2011, 2, 206–214. (b) Song, Z.; Fu, H.; Wang, R.;
Pacheco, L. A.; Wang, X.; Lin, Y.; Cheng, J. Secondary structures
in synthetic polypeptides from N-carboxyanhydrides: design,
modulation, association, and material applications. Chem. Soc.
Rev. 2018, 47, 7401-7425.
(
O
O
these samples, it does not hinder the ability of 2 -7 to
adopt stable -helical conformations, even for 2O and 3O
where sulfoxides are closest to the backbones.
Consequently, the differences in chain conformations
(
5) (a) Poly--amino acids Protein models for conformational
O
O
observed for 2 -7 in water must arise solely from
studies, Fasman, G. D. (ed.), Dekker: New York, New York, 1967.
(b) Lotan, N.; Berger, A.; Katchalski, E. Conformation and
conformational transitions of poly--amino acids in solution.
Annu. Rev. Biochem. 1972, 41, 869-902.
differences in polypeptide solvation.
Here, the synthesis of five new non-ionic, water soluble
sulfoxide containing homopolypeptides, as well as their
incorporation into statistical and block copolymers was
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
6) Pitha, J.; Szente, L.; Greenberg, J. Poly-L-methionine
sulfoxide: a biologically inert analogue of dimethyl sulfoxide
with solubilizing potency. J. Pharm. Sci. 1983, 72, 665–668.
(7) (a) Yu, M.; Nowak, A. P.; Deming, T. J.; Pochan, D. J.
Methylated mono- and diethyleneglycol functionalized
polylysines: Nonionic, -helical, water-soluble polypeptides. J.
Am. Chem. Soc. 1999, 121, 12210–12211. (b) Chen, C.; Wang, Z.; Li,
Z. Thermoresponsive polypeptides from pegylated poly-L-
glutamates. Biomacromolecules 2011, 12, 2859–2863.
O
O
reported. Polypeptides 1 -6 were found to adopt
conformations in water that were dependent on distance
of sulfoxides from the backbone and overall side-chain
lengths. These homologs were found to be a useful model
system for study of helix-coil transitions in water in the
absence of contributions from charged groups or phase
separation. The new amino acid sulfoxides may find use as
hydrophilic guest residues with different conformational
(
8) Hwang, J.; Deming, T. J. Methylated mono- and
di(ethyleneglycol)-functionalized -sheet forming polypeptides.
Biomacromolecules 2001, 2, 17–21.
21
O
preferences in peptide sequences. Also, since 2 has been
shown to be cell and tissue compatible, degradable, and
non-fouling, the new polypeptides here might find use in
biomaterials applications. The ability to select non-ionic,
water soluble polypeptides that are either disordered (e.g.
(9) (a) Bohak, Z.; Katchalski, E. Synthesis, characterization, and
racemization of poly-L-serine. Biochemistry, 1963, 2, 228-237. (b)
Goodman, M.; Felix, A. M. Conformational aspects of
polypeptide structure XIII. A nonionic helical polypeptide in
aqueous solution. Biochemistry, 1964, 3, 1529-1534.
(10) (a) Lupu-Lotan, N.; Yaron, A.; Berger, A.; Sela, M.
Conformation changes in the nonionizable water-soluble
synthetic polypeptide poly-N5-(3-hydroxypropyl)-L-glutamine.
Biopolymers 1965, 3, 625–655. (b) Overgaard, T.; Erie, D.; Darsey,
J. A.; Mattice, W. L. Helix formation by hydroxyamyl-L-
glutaminyl residues in water and aqueous sodium dodecyl
sulfate. Biopolymers 1984, 23, 1595-1603.
(11) (a) Kramer, J. R.; Deming, T. J. Glycopolypeptides with a
redox triggered helix to coil transition. J. Amer. Chem. Soc. 2012,
134, 4112-4115. (b) Fu, X.; Shen, Y.; Fu, W.; Li, Z. Oxidation-
responsive OEGylated poly-L-cysteine and solution properties
studies. Biomacromolecules 2014, 15, 1055–1061.
O
O
2
) or -helical (e.g. 6 ) in water has tremendous potential
22
for controlling block copolymer assembly and in protein
therapeutic stabilization.
23
ASSOCIATED CONTENT
Supporting Information. Supporting figures S1-S6,
experimental procedures and spectral data. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
demingt@seas.ucla.edu Address: Department of
Bioengineering, 5121 Engineering 5, HS-SEAS, University of
California, Los Angeles, CA 90095 Fax: (+1) 310-794-5956
(12) Clark, T.; Murray, J. S.; Lane, P.; Politzer, P. Why are
dimethyl sulfoxide and dimethyl sulfone such good solvents? J.
Mol. Model. 2008, 14, 689–697.
(
13) Kingsbury, C. A.; Day, V. W.; Day, R. O. Conformation in
solution of sterically hindered sulfoxide and sulfone alcohols. J.
Org. Chem. 1980, 45, 5255-5260.
(14) Rodriguez, A. R.; Kramer, J. R.; Deming, T. J. Enzyme-
triggered cargo release from methionine sulfoxide containing
copolypeptide vesicles. Biomacromolecules 2013, 14, 3610–3614.
ACKNOWLEDGMENT
This work was supported by the NSF under MSN 1412367 and
MSN 1807362.
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