2510 Journal of Medicinal Chemistry, 2008, Vol. 51, No. 8
Babaoglu et al.
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spectra were obtained on a Varian 400 MHz NMR. HRMS data
were supplied by The Proteomics and Mass Spectrometry Facility
at NIDDK/NIH/DHHS.
The members of the library were synthesized according to
Scheme S1 (Supporting Information) by a modification of a
previously reported procedure.47 Trimellitic anhydride (1 equiv)
and the appropriate amino acid (1 equiv) were weighed into 0.5–2
mL microwave vials. Diethylene glycol dimethyl ether (diglyme,
0.5 mL) was added to each vial and the vials sealed. The reactions
were heated via microwave irradiation to 200 °C for 10 min and
cooled to room temperature. Reactions were analyzed by LC/MS
and diluted with DMSO (2.5 mL), and the products were purified
to greater than 90% purity by reverse phase preparative HPLC or
LC/MS (acetonitrile/water/0.2% formic acid).
The following modifications were used as necessary: In cases
where amino acids were available as HCl salts, 1 equiv of
triethylamine was added to the reaction mixture. In cases where
reactions were incomplete by LC/MS after 10 min due to insolubil-
ity of the amino acid, an additional 0.5 mL of diglyme was added,
and the reaction heated for a further 10 min at 200 °C, followed
by purification.
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Characterization of molecules synthesized available in Supporting
Information.
Mass Spectroscopy. Protein samples were analyzed by injection
of 1.0 µL onto a Phenomenex Onyx monolithic column (0.1 ×
150 mm) held at 50/50 water/acetonitrile with 0.1% formic acid
added to each solvent. The column flow rate was 1.0 µL/minute.
The column effluent was introduced to an ABI QSTAR XL hybrid
quadrupole orthogonal time-of-flight mass spectrometer equipped
with a MicroIon Spray source. Spray tip voltage was 5.5 kilovolts
and the nebulizing gas value was at 1. The mass spectrometer
analyzed the masses from 500 to 1800 with an accumulation time
of 2.0 s. Typically, several accumulations were averaged to produce
the spectrum acquired. Data analysis and mass determinations were
accomplished using the instrument’s BioAnalyst software.
Accession Codes. The coordinates and structure factors for the
described structures have been deposited in the Protein Data Bank
with the following accession codes: 2PU4 (1), 2PU2 (3), 2R9X
(14), and 2R9W (17).
Acknowledgment. Supported by NIH Grants GM71630 and
GM59957 (to B.K.S.), and a Ruth Kirschstein NRSA fellowship
GM076883 (to K.B.). We thank R. Ferreira for assistance with
cruzain assays. The UCSF Mass Spectrometry Facility (A.
Burlingame, Director) is supported by NIH NCRR BRTP 01614.
B.Y.F. is supported by a Kozloff research fellowship and by a
UCSF School of Pharmacy fellowship.
Supporting Information Available: Schemes and tables detail-
ing chemical characterizations are provided, as is a full table of
the reactive functionality found in the screening library. This
material is available free of charge via the Internet at http://
pubs.acs.org.
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