Reference

Crystal structure of mutant human PIN1 peptidyl-prolyl isomerase and ligand complexes, and their use for drug discovery

Crystal structure of mutant human PIN1 peptidyl-prolyl isomerase and ligand complexes, and their use for drug discovery. Matthews, David Allan; Dagostino, Eleanor Ferronyalka; Ferre, Rose Ann; Gaur, Smita; Guo, Chuangxing; Hou, Xinjun; Margosiak, Stephen; Mroczkowski, Barbara; Nakayama, Grace Reiko; Parge, Hans Erich; Zhu, Jeff Xianchao (Pfizer Inc., USA). PCT Int. Appl. WO 2004005315 A2 15 Jan 2004, 63 pp. DESIGNATED STATES: W: AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NI, NO, NZ, OM, PH, PL, PT, RO, RU, SC, SD, SE, SG, SK, SL, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, YU, ZA, ZM, ZW, AM, AZ, BY, KG, KZ, MD, RU, TJ, TM; RW: AT, BE, BF, BJ, CF, CG, CH, CI, CM, CY, DE, DK, ES, FI, FR, GA, GB, GR, IE, IT, LU, MC, ML, MR, NE, NL, PT, SE, SN, TD, TG, TR. (English).Several reagents with their cas registry numbers 415965-81-0 and 5267-64-1 are used here. (World Intellectual Property Organization). CODEN: PIXXD2. CLASS: ICM: C07K. APPLICATION: WO 2003-IB3101 27 Jun 2003. PRIORITY: US 2002-PV394889 9 Jul 2002. DOCUMENT TYPE: Patent CA Section: 7 (Enzymes) Section cross-reference(s): 1, 3, 13, 63, 75 Polypeptides contg. the human PIN1 peptidyl-prolyl isomerase domain but not contg. the PIN1 WW domain are described. Also described are crystal structures of these polypeptides, including the crystal structure of a PIN1 PPlase ligand complex. The structure coordinate data derived from these crystals provides a three-dimensional description of the substrate-binding site of PIN1 peptidyl-prolyl isomerase useful in drug discovery and design for the identification and design of modulators of PIN1 peptidyl-prolyl isomerase activity. .

Chiral lipophilic ligands

Chiral lipophilic ligands. 5. Enantioselective ester cleavage of a-amino esters by Cu(II) complexes of chiral diamino alcohols in aqueous surfactant solutions. Cleij, Marco C.; Mancin, Fabrizio; Scrimin, Paolo; Tecilla, Paolo; Tonellato, Umberto (Dep. Organic Chemistry, Univ. Padova, Padua I-35131, Italy). Tetrahedron, 53(1), 357-368 (English) 1997 Elsevier. CODEN: TETRAB. ISSN: 0040-4020. DOCUMENT TYPE: Journal CA Section: 34 (Amino Acids, Peptides, and Proteins) Section cross-reference(s): 7, 22, 66, 67, 78 Lipophilic ligands, 1-3 (shown as I; R1 = H R2 = H3C, (H3C)2CH, (H3C)2CHCH2, PhCH2, R3 = H (1); R1 = H3C, R2 = PhCH2, R3 = H (2); R1 = H, R2 = PhCH2; R3 = H3C (3)) featuring an 1,2-ethylenediamino moiety as chelating subunit, one (1,3) or two (2) chiral carbons, and an hydroxy function (except for 3) in the proximity of the coordination center, were synthesized. Their Cu(II) complexes were studied as catalysts for the cleavage of p-nitrophenyl esters of phenylalanine (PhePNP) and phenylglycine (PhgPNP) in the presence of cationic aggregates formed by cetyltrimethylammonium bromide (CTABr) or ditetradecyldibutylammonium bromide (DMDBAB). Large rate accelerations (up to two orders of magnitude) and quite remarkable enantioselectivities (from 11 to 35, as the ratios of the rate consts. 7533-40-6 is the cas registry number of certain chemical which is used as reagents here. measured for the faster and slower reacting enantiomers) were obsd. In the case of ligands 1 the S-ligand complex reacts faster with the S-substrate and the enantioselectivity increases with the lipophilicity of the substituent of the chiral carbons. Using ligands 2, having two chiral centers, the most favored situation is reached when all the chiral carbons of ligands and substrate have the same abs. configuration; in such a case, and using DMDBAB as cosurfactant, enantioselectivities ￡35 were obsd. The results are explained from a different reaction mechanism due to the compartmentalization of the reacting species (a ternary complex ligand/Cu(II)/substrate) in different loci of the aggregate. Probably depending on the hydrophobicity of the ternary complex, the effective nucleophile may switch from the Cu(II)-bound ligand's hydroxyl to a Cu(II) bound H2O mol. The 1st mechanism is faster and prevails for the more lipophilic ternary complex. .