Sökning: onr:"swepub:oai:DiVA.org:liu-46676" > Optimization of P1-...
Fältnamn | Indikatorer | Metadata |
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000 | 06333naa a2200637 4500 | |
001 | oai:DiVA.org:liu-46676 | |
003 | SwePub | |
008 | 091011s2003 | |||||||||||000 ||eng| | |
009 | oai:DiVA.org:uu-48472 | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-466762 URI |
024 | 7 | a https://doi.org/10.1046/j.1432-1033.2003.03533.x2 DOI |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-484722 URI |
040 | a (SwePub)liud (SwePub)uu | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Andersson, H.O.u Uppsala universitet,Institutionen för naturvetenskaplig biokemi,Institutionen för cell- och molekylärbiologi,Biokemi, Mannervik,Inst. of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden,Dept. of Organ. Pharmaceutical Chem., Uppsala University, Uppsala, Sweden4 aut |
245 | 1 0 | a Optimization of P1-P3 groups in symmetric and asymmetric HIV-1 protease inhibitors |
264 | 1 | b Wiley,c 2003 |
338 | a print2 rdacarrier | |
520 | a HIV-1 protease is an important target for treatment of AIDS, and efficient drugs have been developed. However, the resistance and negative side effects of the current drugs has necessitated the development of new compounds with different binding patterns. In this study, nine C-terminally duplicated HIV-1 protease inhibitors were cocrystallised with the enzyme, the crystal structures analysed at 1.8-2.3 Å resolution, and the inhibitory activity of the compounds characterized in order to evaluate the effects of the individual modifications. These compounds comprise two central hydroxy groups that mimic the geminal hydroxy groups of a cleavage-reaction intermediate. One of the hydroxy groups is located between the d-oxygen atoms of the two catalytic aspartic acid residues, and the other in the gauche position relative to the first. The asymmetric binding of the two central inhibitory hydroxyls induced a small deviation from exact C2 symmetry in the whole enzyme-inhibitor complex. The study shows that the protease molecule could accommodate its structure to different sizes of the P2/P2' groups. The structural alterations were, however, relatively conservative and limited. The binding capacity of the S3/S3' sites was exploited by elongation of the compounds with groups in the P3/P3' positions or by extension of the P1/P1' groups. Furthermore, water molecules were shown to be important binding links between the protease and the inhibitors. This study produced a number of inhibitors with Ki values in the 100 picomolar range. | |
650 | 7 | a NATURVETENSKAPx Biologix Biokemi och molekylärbiologi0 (SwePub)106022 hsv//swe |
650 | 7 | a NATURAL SCIENCESx Biological Sciencesx Biochemistry and Molecular Biology0 (SwePub)106022 hsv//eng |
653 | a AIDS | |
653 | a Drug | |
653 | a HIV | |
653 | a Protease | |
653 | a X-ray | |
653 | a TECHNOLOGY | |
653 | a TEKNIKVETENSKAP | |
653 | a Biochemistry | |
700 | 1 | a Fridborg, K.u Uppsala universitet,Institutionen för cell- och molekylärbiologi,Inst. of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden4 aut |
700 | 1 | a Lowgren, S.u Uppsala universitet,Institutionen för cell- och molekylärbiologi,Löwgren, S., Inst. of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden4 aut |
700 | 1 | a Alterman, M.u Uppsala universitet,Avdelningen för organisk farmaceutisk kemi,Dept. of Organ. Pharmaceutical Chem., Uppsala University, Uppsala, Sweden,Mühlman, A., Department of Organic Chemistry, Stockholm University, Stockholm, Sweden4 aut |
700 | 1 | a Muhlman, A.u Mühlman, A., Department of Organic Chemistry, Stockholm University, Stockholm, Sweden4 aut |
700 | 1 | a Bjorsne, M.u Björsne, M., Department of Organic Chemistry, Stockholm University, Stockholm, Sweden4 aut |
700 | 1 | a Garg, N.u Uppsala universitet,Avdelningen för organisk farmaceutisk kemi,Dept. of Organ. Pharmaceutical Chem., Uppsala University, Uppsala, Sweden4 aut |
700 | 1 | a Kvarnström, Ingemaru Linköpings universitet,Tekniska högskolan,Organisk Kemi4 aut0 (Swepub:liu)ingkv34 |
700 | 1 | a Schaal, Wesleyu Uppsala universitet,Avdelningen för organisk farmaceutisk kemi,Dept. of Organ. Pharmaceutical Chem., Uppsala University, Uppsala, Sweden4 aut0 (Swepub:uu)weslscha |
700 | 1 | a Classon, B.u Department of Organic Chemistry, Stockholm University, Stockholm, Sweden4 aut |
700 | 1 | a Karlen, A.u Uppsala universitet,Avdelningen för organisk farmaceutisk kemi,Karlén, A., Dept. of Organ. Pharmaceutical Chem., Uppsala University, Uppsala, Sweden4 aut |
700 | 1 | a Danielson, U. Helenau Uppsala universitet,Institutionen för naturvetenskaplig biokemi,Department of Biochemistry, Uppsala University, Uppsala, Sweden4 aut0 (Swepub:uu)helenads |
700 | 1 | a Ahlsen, G.u Uppsala universitet,Institutionen för naturvetenskaplig biokemi,Ahlsén, G., Department of Biochemistry, Uppsala University, Uppsala, Sweden4 aut |
700 | 1 | a Nillroth, U.u Uppsala universitet,Institutionen för naturvetenskaplig biokemi,Department of Biochemistry, Uppsala University, Uppsala, Sweden4 aut |
700 | 1 | a Vrang, L.u Medivir AB, Lunastigen 7, Huddinge, Sweden4 aut |
700 | 1 | a Oberg, B.u Öberg, B., Medivir AB, Lunastigen 7, Huddinge, Sweden4 aut |
700 | 1 | a Samuelsson, B.u Department of Organic Chemistry, Stockholm University, Stockholm, Sweden4 aut |
700 | 1 | a Hallberg, A.u Uppsala universitet,Avdelningen för organisk farmaceutisk kemi4 aut |
700 | 1 | a Unge, T.u Uppsala universitet,Institutionen för cell- och molekylärbiologi,Inst. of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden, Inst. of Cell and Molecular Biology, Box 590, Uppsala University, SE-751 24 Uppsala, Sweden4 aut |
710 | 2 | a Uppsala universitetb Institutionen för naturvetenskaplig biokemi4 org |
773 | 0 | t European Journal of Biochemistryd : Wileyg 270:8, s. 1746-1758q 270:8<1746-1758x 0014-2956x 1432-1033 |
856 | 4 | u https://febs.onlinelibrary.wiley.com/doi/pdfdirect/10.1046/j.1432-1033.2003.03533.x |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-46676 |
856 | 4 8 | u https://doi.org/10.1046/j.1432-1033.2003.03533.x |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-48472 |
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