Journal of Medicinal Chemistry
Article
set to 1−2 s. The X-ray beam with size of 0.07 × 0.20 mm2 was
adjusted to pass through the centers of the capillaries for every
measurement. In order to obtain good signal-to-noise ratios, 20 images
were taken for each sample and buffer. The 2-D scattering images were
converted to 1-D SAXS curves, i.e., intensity (I(q)) vs q, through
azimuthally averaging after solid angle correction and then normalizing
with the intensity of the transmitted X-ray beam, using the software
package developed at beamline 12ID-B.
Enzymatic Stability Study. Compound 7 and peptide control
AcVQIVYK (1 mg/mL) were incubated with 0.1 mg/mL Pronase in
100 mM ammonium bicarbonate buffer (pH 7.8) at 37 °C for 18 h.
The reaction mixtures were concentrated in a speed vacuum at 60 °C
to remove water and ammonium bicarbonate. The resulting residues
were redissolved in water and analyzed on a Waters analytical HPLC
system with 1 mL/min flow rate and 5% to 100% linear gradient of
solvent B (0.1% TFA in acetonitrile) in A (0.1% TFA in water) over
the duration of 40 min. The UV detector was set to 215 nm.
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ASSOCIATED CONTENT
* Supporting Information
■
S
Synthesis and characterization of compounds, MIC, hemolytic
activity, time-kill study, fluorescent microscopy. The Support-
ing Information is available free of charge on the ACS
AUTHOR INFORMATION
Corresponding Author
■
Notes
The authors declare no competing financial interest.
(19) Niu, Y.; Hu, Y.; Li, X.; Chen, J.; Cai, J. [gamma]-AApeptides:
design, synthesis and evaluation. New J. Chem. 2011, 35, 542−545.
(20) Yang, Y.; Niu, Y.; Hong, H.; Wu, H.; Zhang, Y.; Engle, J.;
Barnhart, T.; Cai, J.; Cai, W. Radiolabeled gamma-AApeptides: a new
class of tracers for positron emission tomography. Chem. Commun.
2012, 48, 7850−7852.
(21) Wu, H.; Li, Y.; Ge, B.; Niu, Y.; Qiao, Q.; Tipton, J.; Cao, C.; Cai,
J. γ-AApeptide-based small-molecule ligands that disrupt Aβ
aggregation. Chem. Commun. 2014, 50, 5206−5208.
(22) Niu, Y.; Wu, H.; Li, Y.; Hu, Y.; Padhee, S.; Li, Q.; Cao, C.; Cai,
J. AApeptides as a new class of antimicrobial agents. Org. Biomol.
Chem. 2013, 11, 4283−4290.
ACKNOWLEDGMENTS
This work is supported by NSF CAREER 1351265.
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ABBREVIATIONS USED
■
HDP, host-defense peptide; MIC, minimum inhibitory
concentration; DCM, dichloromethane; DMF, N,N-dimethyl-
formamide; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-
trazolium bromide; NMR, nuclear magnetic resonance; SAXS,
small-angle X-ray scattering
(23) Wu, H.; Niu, Y.; Padhee, S.; Wang, R. E.; Li, Y.; Qiao, Q.; Ge,
B.; Cao, C.; Cai, J. Design and synthesis of unprecedented cyclic
gamma-AApeptides for antimicrobial development. Chem. Sci. 2012, 3,
2570−2572.
(24) Niu, Y.; Padhee, S.; Wu, H.; Bai, G.; Harrington, L.; Burda, W.
N.; Shaw, L. N.; Cao, C.; Cai, J. Identification of gamma-AApeptides
with potent and broad-spectrum antimicrobial activity. Chem.
Commun. 2011, 47, 12197−12199.
(25) Niu, Y.; Padhee, S.; Wu, H.; Bai, G.; Qiao, Q.; Hu, Y.;
Harrington, L.; Burda, W. N.; Shaw, L. N.; Cao, C.; Cai, J. Lipo-
gamma-AApeptides as a new class of potent and broad-spectrum
antimicrobial agents. J. Med. Chem. 2012, 55, 4003−4009.
(26) Li, Y.; Smith, C.; Wu, H.; Padhee, S.; Manoj, N.; Cardiello, J.;
Qiao, Q.; Cao, C.; Yin, H.; Cai, J. Lipo-gamma-AApeptides as a new
class of potent and broad-spectrum antimicrobial agents. ACS Chem.
Biol. 2014, 9, 211−217.
(27) Thaker, H. D.; Som, A.; Ayaz, F.; Lui, D. H.; Pan, W. X.; Scott,
R. W.; Anguita, J.; Tew, G. N. Synthetic mimics of antimicrobial
peptides with immunomodulatory responses. J. Am. Chem. Soc. 2012,
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