chemia - Studia

More documents

Recommendations

Info

X-RAY CRYSTAL STRUCTURE AND DYNAMICS REVEAL HIV-1 PROTEASE DRUG INTERACTIONS RESULTS AND DISCUSSION Four multi-drug resistant HIV-1 protease isolates are resistant to inhibitors at various levels HIV-1 protease NL4-3 Table 1. Sequences of HIV-1 protease variants Sequences* PQITLWKRPL VTIKIGGQLK EALLDTGADD TVLEEMNLPG RWKPKMIGGI GGFIKVRQYD QILIEICGHK AIGTVLVGPT PVNIIGRNLL TQIGCTLNF 769 PQITLWKRPI VTIKIGGQLK EALLDTGADD TVLEEVNLPG RWKPKLIGGI GGFVKVRQYD QVPIEICGHK VIGTVLVGPT PANVIGRNLM TQIGCTLNF 807 PQITLWKRPI VTIKIGGQLK EALLDTGADD TVLEEMNLPG KWKPKIIVGI GGFTKVRQYD NVQIEICGHK VIGAVLIGPT PANIIGRNLL TQLGCTLNF 1385 PQITLWKRPF VTIKIGGQLK EALLDTGADD TVLEEIDLPG RWKPKIIGGI GGFIKVKQYD QIPIEICGHK VIGTVLVGPT PTNIIGRNMM TQLGCTLNF 3761 PQITLWKRPI VAIKVGGQII EALLDTGADD TVLEEMNLPG RWKPKIIGGI GGFIKVRQYD QIPVEICGHK IITTVLVGST PVNVIGRNLM TQLGCTLNF *The polymorphic changes are underlined. The drug-resistance mutations are highlighted in red. Figure 2. Fold resistance of four multi-drug resistant HIV-1 protease variants. 223
YONG WANG, TAMARIA G. DEWDNEY, ZHIGANG LIU, SAMUEL J. REITER, ET ALL Four MDR HIV-1 protease variants were isolated by Palmer et al. from patients failing protease inhibitor-containing antiretroviral regimens (Table 1) [8]. The drug-resistance profiles of four clinical MDR HIV-1 protease isolates were identified using enzyme inhibition assays. Four MDR protease variants were resistant to all FDA-approved HIV-1 protease inhibitors at various levels (Figure 2). The second generation of HIV-1 protease inhibitors (darunavir, atazanavir, lopinavir, and tipranavir) encountered relatively lower fold resistance. Among the four MDR protease variants tested here, MDR 807 and MDR 1385 were more resistant to the second generation HIV-1 protease inhibitors. According to the guidelines for the use of antiretroviral agents in HIV-1- infected adults and adolescents, darunavir and atazanavir are preferred first-line antiretroviral drugs [9]. Our results showed that there was higher resistance to atazanavir comparing to darunavir. These results confirmed the in vitro resistance observed of the clinical isolates of HIV-1 protease. Potent inhibitors induced flap closure of the multi-drug resistant HIV-1 protease Ile50 Ile50 A B Figure 3. The hydrogen bonds between HIV-1 protease flaps and inhibitors. (A) tipranavir-MDR 769 complex structure. (B) darunavir-MDR 769 complex structure. The hydrogen bonds are represented as blue dash lines. The bridging water molecule is represented in a red dot. Darunavir and tipranavir are among the protease inhibitors exhibiting the most potency and least fold resistance. The tipranavir-MDR 769 82T complex crystallized in the hexagonal space group P6 1 while the darunavir- MDR 769 82T complex crystallized in the orthorhombic space group P2 1 2 1 2 1 . The crystal structure was determined at 1.24 Å resolution and 2.87 Å resolution, respectively. The other seven FDA-approved HIV-1 protease inhibitors crystallized with MDR 769 in an open form. The binding of tipranavir or darunavir effectively closes the open flaps of MDR 769. Tipranavir directly interacts with Ile50 while darunavir interacts with Ile50 through a bridging 224
Page 1 and 2:
CHEMIA 3/2011
Page 3 and 4:
CORINA COSTESCU, LAURA CORPAŞ, NIC
Page 5 and 6:
Studia Universitatis Babes-Bolyai C
Page 7 and 8:
MONICA BAIA, MONICA SCARISOREANU, I
Page 9 and 10:
Page 11 and 12:
Page 13 and 14:
Page 16 and 17:
STUDIA UBB CHEMIA, LVI, 3, 2011 (p.
Page 18 and 19:
PREPARATION, CHARACTERIZATION AND S
Page 20 and 21:
Page 22 and 23:
Page 24 and 25:
Page 26 and 27:
Page 28 and 29:
Page 30 and 31:
SPECTROSCOPIC EVIDENCE OF COLLAGEN
Page 32 and 33:
Page 34:
Page 37 and 38:
CORNEL-VIOREL POP, TRAIAN ŞTEFAN,
Page 39 and 40:
Page 41 and 42:
Page 43 and 44:
Page 45 and 46:
VITALY ERUKHIMOVITCH, IGOR MUKMANOV
Page 47 and 48:
Page 49 and 50:
Page 51 and 52:
Page 53 and 54:
DUMITRU GEORGESCU, ZSOLT PAP, MONIC
Page 55 and 56:
Page 57 and 58:
Page 59 and 60:
Page 61 and 62:
MAHDIEH AZARI, ALI IRANMANESH DEFIN
Page 63 and 64:
MAHDIEH AZARI, ALI IRANMANESH V ( G
Page 65 and 66:
MAHDIEH AZARI, ALI IRANMANESH Now,
Page 67 and 68:
MAHDIEH AZARI, ALI IRANMANESH Let T
Page 69 and 70:
MAHDIEH AZARI, ALI IRANMANESH Let G
Page 71 and 72:
MAHDIEH AZARI, ALI IRANMANESH ACKNO
Page 73 and 74:
CRISTINA GRUIAN, HEINZ-JÜRGEN STEI
Page 75 and 76:
Page 77 and 78:
Page 79 and 80:
Page 81 and 82:
Page 84 and 85:
Page 86 and 87:
CYCLODEXTRINS AND SMALL UNILAMELLAR
Page 88 and 89:
CYCLODEXTRINS AND SMALL UNILAMELLAR
Page 90 and 91:
Page 92 and 93:
PROTEIN ADHESION TO BIOACTIVE MICRO
Page 94 and 95:
Page 96 and 97:
Page 98 and 99:
Page 100 and 101:
LC/MS ANALYSIS OF STEROLIC COMPOUND
Page 102 and 103:
LC/MS ANALYSIS OF STEROLIC COMPOUND
Page 104 and 105:
Page 106 and 107:
INVESTIGATION OF THE EFFECTS OF DEG
Page 108 and 109:
Page 110 and 111:
Page 112 and 113:
Page 114 and 115:
PM3 CONFORMATIONAL ANALYSIS OF THE
Page 116 and 117:
Page 118 and 119:
Page 120 and 121:
Page 122 and 123:
Page 124 and 125:
Page 126 and 127:
Page 128:
Page 131 and 132:
MIHAELA POP, STEFAN TRAIAN, LIVIU D
Page 133 and 134:
Page 135 and 136:
Page 137 and 138:
DIMITRI A. SVISTUNENKO, MARY ADELUS
Page 139 and 140:
Page 141 and 142:
Page 143 and 144:
Page 145 and 146:
Page 147 and 148:
Page 149 and 150:
MILICA TODEA, TEODORA MARCU, MONICA
Page 151 and 152:
Page 153 and 154:
Page 155 and 156:
Page 157 and 158:
Page 159 and 160:
EDINA DORDAI, DANA ALINA MĂGDAŞ,
Page 161 and 162:
Page 163 and 164:
Page 166 and 167:
Page 168 and 169:
UV ABSORPTION PROPERTIES OF DOPED P
Page 170:
UV ABSORPTION PROPERTIES OF DOPED P
Page 173 and 174: HASTI ATEFI, MAHMOOD GHORANNEVISS,
Page 181 and 182: LUCIANA UDRESCU, BOGDAN MARTA, MIHA
Page 187 and 188: ALI MADANSHEKAF, MARJAN MORADI wher
Page 189 and 190: ALI MADANSHEKAF, MARJAN MORADI and
Page 191 and 192: ALI MADANSHEKAF, MARJAN MORADI Agai
Page 193 and 194: ALI MADANSHEKAF, MARJAN MORADI 9. M
Page 195 and 196: ROZALIA VERES, CONSTANTIN CIUCE, VI
Page 202 and 203: STUDIA UBB CHEMIA, LVI, 3, 2011 (p.
Page 204 and 205: EVALUATION OF FREE RADICAL CONCENTR
Page 206 and 207: EVALUATION OF FREE RADICAL CONCENTR
Page 210 and 211: ECCENTRIC CONNECTIVITY INDEX OF TOR
Page 212: ECCENTRIC CONNECTIVITY INDEX OF TOR
Page 215 and 216: DORINA GIRBOVAN, MARIUS AUREL BODEA
Page 223: YONG WANG, TAMARIA G. DEWDNEY, ZHIG
Page 227 and 228: YONG WANG, TAMARIA G. DEWDNEY, ZHIG
Page 233 and 234: ALEXANDRU LUPAN, CSONGOR MATYAS, AU
Page 241 and 242: EMILIA VANEA, SIMONA CAVALU, FLORIN
Page 249 and 250: ANDRA TĂMAŞ, MARTIN VINCZE The ma
Page 251 and 252: ANDRA TĂMAŞ, MARTIN VINCZE From t
Page 253 and 254: ANDRA TĂMAŞ, MARTIN VINCZE 2%B +
Page 255 and 256: ANDRA TĂMAŞ, MARTIN VINCZE increa
Page 260 and 261: EFFECT OF CATALYST LAYER THICKNESS
Page 268 and 269: SPECTRAL INVESTIGATIONS AND DFT STU
Page 274 and 275:
Page 276 and 277:
TOPOLOGICAL SYMMETRY OF TWO FAMILIE
Page 278 and 279:
TOPOLOGICAL SYMMETRY OF TWO FAMILIE
Page 280 and 281:
Page 282 and 283:
NEW 1-AZABICYCLO[3.2.2]NONANE DERIV
Page 284 and 285:
Page 286 and 287:
show all

chemia - Studia

Create successful ePaper yourself

Delete template?

Save as template?