2OO8

Synthesis, Structural Analysis, and SAR Studies of Triazine Derivatives as Potent, Selective Tie-2 Inhibitors

X-RAY DIFFRACTION

Crystallization

Crystalization Experiments
ID	Method	pH	Temperature	Details
1	VAPOR DIFFUSION, HANGING DROP	7	298	14-18 % (w/v) PEG 3350, and 0.2 M tri-Potassium Citrate (pH 6.5-7.5), and 2% (v/v) isopropanol, pH 7.0, VAPOR DIFFUSION, HANGING DROP, temperature 298K

Crystal Properties
Matthews coefficient	Solvent content
2.45	49.71

Crystal Data

Unit Cell
Length ( Å )	Angle ( ˚ )
a = 62.604	α = 90
b = 62.604	β = 90
c = 181.043	γ = 90

Symmetry
Space Group	P 41 21 2

Diffraction

Diffraction Experiment
ID #	Crystal ID	Scattering Type	Data Collection Temperature	Detector	Detector Type	Details	Collection Date	Monochromator	Protocol
1	1	x-ray	100	IMAGE PLATE	RIGAKU RAXIS IV	osmic	2003-06-17	M	SINGLE WAVELENGTH

Radiation Source
ID #	Source	Type	Wavelength List	Synchrotron Site	Beamline
1	ROTATING ANODE	RIGAKU RU200	1.5418

Data Collection

Overall
ID #	Resolution (High)	Resolution (Low)	Percent Possible (Observed)	R Merge I (Observed)	Net I Over Average Sigma (I)	Redundancy	Number Reflections (All)	Number Reflections (Observed)	Observed Criterion Sigma (F)	Observed Criterion Sigma (I)	B (Isotropic) From Wilson Plot
1	2.2	35	98.9	0.038	18.8		18140	17941	-1	-1

Highest Resolution Shell
ID #	Resolution (High)	Resolution (Low)	Percent Possible (All)	Percent Possible (Observed)	R Merge I (Observed)	Mean I Over Sigma (Observed)	Redundancy	Number Unique Reflections (All)
	2.2	2.28	98		0.265	5.7	6	1822

Refinement

Statistics
Diffraction ID	Structure Solution Method	Cross Validation method	Resolution (High)	Resolution (Low)	Number Reflections (All)	Number Reflections (Observed)	Number Reflections (R-Free)	Percent Reflections (Observed)	R-Factor (Observed)	R-Work	R-Free	R-Free Selection Details	Mean Isotropic B
X-RAY DIFFRACTION	MOLECULAR REPLACEMENT	THROUGHOUT	2.2	59.13	18140	17941	971	98.91	0.23542	0.23318	0.27862	RANDOM	39.787

Temperature Factor Modeling
Anisotropic B[1][1]	Anisotropic B[1][2]	Anisotropic B[1][3]	Anisotropic B[2][2]	Anisotropic B[2][3]	Anisotropic B[3][3]
1.16			1.16		-2.32

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	32.515
r_dihedral_angle_4_deg	20.007
r_dihedral_angle_3_deg	14.554
r_dihedral_angle_1_deg	5.48
r_scangle_it	2.65
r_scbond_it	1.729
r_mcangle_it	1.212
r_angle_refined_deg	1.206
r_mcbond_it	0.699
r_nbtor_refined	0.3

RMS Deviations
Key	Refinement Restraint Deviation
r_dihedral_angle_2_deg	32.515
r_dihedral_angle_4_deg	20.007
r_dihedral_angle_3_deg	14.554
r_dihedral_angle_1_deg	5.48
r_scangle_it	2.65
r_scbond_it	1.729
r_mcangle_it	1.212
r_angle_refined_deg	1.206
r_mcbond_it	0.699
r_nbtor_refined	0.3
r_symmetry_hbond_refined	0.202
r_nbd_refined	0.191
r_xyhbond_nbd_refined	0.151
r_symmetry_vdw_refined	0.13
r_chiral_restr	0.076
r_bond_refined_d	0.011
r_gen_planes_refined	0.005

Non-Hydrogen Atoms Used in Refinement
Non-Hydrogen Atoms	Number
Protein Atoms	2000
Nucleic Acid Atoms
Solvent Atoms	121
Heterogen Atoms	39

Software

Software
Software Name	Purpose
REFMAC	refinement
CrystalClear	data collection
DENZO	data reduction
SCALEPACK	data scaling
AMoRE	phasing

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.