Minimising the payload solvent exposed hydrophobic surface area optimises the antibody-drug conjugate properties
Hobson, Adrian D.; Zhu, Haizhong; Qiu, Wei; Judge, Russell; Longenecker, Kenton; RSC Medicinal Chemistry  (2024) –; doi:10.1039/D3MD00540B

data_7247985
_publ_section_title
;
 Minimising the payload solvent exposed hydrophobic surface area optimises
 the antibody-drug conjugate properties
;
_journal_name_full               'RSC Medicinal Chemistry'
_journal_paper_doi               10.1039/D3MD00540B
_journal_year                    2024
_chemical_absolute_configuration ad
_chemical_formula_sum            'C35.5 H40 Cl N O6'
_chemical_formula_weight         612.13
_space_group_crystal_system      monoclinic
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_atom_sites_solution_hydrogens   mixed
_audit_block_doi                 10.5517/ccdc.csd.cc2gxcpg
_audit_creation_method           SHELXL-2018/3
_audit_update_record
;
2023-08-28 deposited with the CCDC.	2024-01-08 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 102.751(4)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   7.6256(6)
_cell_length_b                   28.525(2)
_cell_length_c                   14.6246(11)
_cell_measurement_reflns_used    9722
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      65.0595
_cell_measurement_theta_min      3.98
_cell_volume                     3102.7(4)
_computing_cell_refinement
'Apex3 v2019.11-0 (Bruker Nano, 2019-2020, Bruker Nonius 2003-2004, Bruker AXS 2005-2018)'
_computing_data_collection
'Apex3 v2019.11-0 (Bruker Nano, 2019-2020, Bruker Nonius 2003-2004, Bruker AXS 2005-2018)'
_computing_data_reduction
'Apex3 v2019.11-0 (Bruker Nano, 2019-2020, Bruker Nonius 2003-2004, Bruker AXS 2005-2018)'
_computing_molecular_graphics    'ORTEP-3 for Windows v2.01'
_computing_publication_material  'SHELXL-97 (Sheldrick, 2008)'
_computing_structure_refinement  'SHELXL-2018/3 (Sheldrick, 2018)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_temperature      100(2)
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.998
_diffrn_measurement_device_type  CPAD
_diffrn_measurement_method       'omega-phi scan'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0732
_diffrn_reflns_av_unetI/netI     0.0424
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.998
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       33
_diffrn_reflns_limit_k_min       -33
_diffrn_reflns_limit_l_max       17
_diffrn_reflns_limit_l_min       -17
_diffrn_reflns_number            73585
_diffrn_reflns_point_group_measured_fraction_full 0.996
_diffrn_reflns_point_group_measured_fraction_max 0.996
_diffrn_reflns_theta_full        65.334
_diffrn_reflns_theta_max         65.334
_diffrn_reflns_theta_min         3.098
_diffrn_source                   'sealed tube'
_exptl_absorpt_coefficient_mu    1.477
_exptl_absorpt_correction_type   multi-scan
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.310
_exptl_crystal_density_meas      ?
_exptl_crystal_description       block
_exptl_crystal_F_000             1300
_exptl_crystal_size_max          0.400
_exptl_crystal_size_mid          0.200
_exptl_crystal_size_min          0.020
_exptl_transmission_factor_max   0.7526
_exptl_transmission_factor_min   0.5668
_refine_diff_density_max         0.474
_refine_diff_density_min         -0.306
_refine_diff_density_rms         0.042
_refine_ls_abs_structure_details
;
 Flack x determined using 4474 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.003(9)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.052
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     818
_refine_ls_number_reflns         10585
_refine_ls_number_restraints     14
_refine_ls_restrained_S_all      1.054
_refine_ls_R_factor_all          0.0454
_refine_ls_R_factor_gt           0.0411
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0443P)^2^+1.5477P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0987
_refine_ls_wR_factor_ref         0.1013
_reflns_Friedel_coverage         0.953
_reflns_Friedel_fraction_full    0.994
_reflns_Friedel_fraction_max     0.994
_reflns_number_gt                9942
_reflns_number_total             10585
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3md00540b1.cif
_cod_data_source_block           compound17
_cod_depositor_comments
;
The following automatic conversions were performed:

data item '_exptl_crystal_density_meas' value 'none' was changed to
'?' -- the value is perceived as not measured.

Automatic conversion script
Id: cif_fix_values 8170 2020-07-09 18:12:32Z antanas 
;
_cod_original_sg_symbol_H-M      'P 21'
_cod_original_formula_sum        'C35.50 H40 Cl N O6'
_cod_database_code               7247985
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_min   0.590
_shelx_estimated_absorpt_t_max   0.971
_shelx_res_checksum              98620