Structure-based design of C8-substituted O6-cyclohexylmethoxyguanine CDK1 and 2 inhibitors.

8-Substituted O6-Cyclohexylmethylguanine Cdk2 Inhibitors; Using Structure-Based Inhibitor Design to Optimise an Alternative Binding Mode.

CDK-ACTIVATING FRAGMENT, RESIDUES 175-432

CELL DIVISION PROTEIN KINASE 2, P33 PROTEIN KINASE

GPGSMENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNHPNIVKLLDVIHTENKL
YLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPV
RTY(TPO)HEVVTLWYRAPEILLGCKYYSTAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTS
MPDYKPSFPKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL

GPGSMENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNHPNIVKLLDVIHTENKL
YLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPV
RTYTHEVVTLWYRAPEILLGCKYYSTAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDY
KPSFPKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL

VPDYHEDIHTYLREMEVKCKPKVGYMKKQPDITNSMRAILVDWLVEVGEEYKLQNETLHLAVNYIDRFLSSMSVLRGKLQ
LVGTAAMLLASKFEEIYPPEVAEFVYITDDTYTKKQVLRMEHLVLKVLTFDLAAPTVNQFLTQYFLHQQPANCKVESLAM
FLGELSLIDADPYLKYLPSVIAGAAFHLALYTVTGQSWPESLIRKTGYTLESLKPCLMDLHQTYLKAPQHAQQSIREKYK
NSKYHGVSLLNPPETLNL

50 MM AMMONIUM ACETATE, 10% PEG-3350, 15 MM NACL, 100 MM HEPES, PH = 7.4, 10% DMSO

CO-CRYSTAL STRUCTURE OF 6-CYCLOHEXYLMETHOXY-8-ISOPROPYL -9H-PURIN-2-YLAMINE AND MONOMERIC CDK2

STRUCTURE-BASED DESIGN OF C8-SUBSTITUTED O6- CYCLOHEXYLMETHOXYGUANINE CDK1 AND 2 INHIBITORS.

HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS.

CELL CYCLE, CYCLIN DEPENDENT KINASES, STRUCTURE-BASED DRUG DESIGN, CONFORMATIONAL RESTRAINT, REVERSED BINDING MODE