HIV-1 protease inhibition potential of functionalized polyoxometalates.
Polyoxometalates (POMs) are interesting biomedical agents due to their versatile anticancer and antiviral properties, such as remarkable anti-HIV activity. Although POMs are tunable and easily accessible inorganic drug prototypes in principle, their full potential can only be tapped by enhancing their biocompatibility, for example, through organic functionalization. We have therefore investigated the HIV-1 protease inhibition potential of functionalized Keggin- and Dawson-type POMs with organic side chains. Their inhibitory performance was furthermore compared to other POM types, and the buffer dependence of the results is discussed. In addition, chemical shift mapping NMR experiments were performed to exclude POM-substrate interactions. Whereas the introduction of organic side chains into POMs is a promising approach in principle, the influence of secondary effects on the reaction system also merits detailed investigation.
Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Andreas
A
Flütsch
Thilo
T
Schroeder
Markus G
MG
Grütter
Greta R
GR
Patzke
D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D011485:Protein Binding; D013055:Spectrophotometry, Infrared; D017973:Tungsten Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000099294:Polyoxometalates
D016333:HIV Protease; D017320:HIV Protease Inhibitors; D017973:Tungsten Compounds; C102296:polyoxometalate I; D000099294:Polyoxometalates; C514803:p16 protease, Human immunodeficiency virus 1
J Am Chem Soc. 2001 Feb 7;123(5):886-97
11456622
Biol Chem. 2003 Jul;384(7):1109-17
12956428
Antiviral Res. 2003 May;58(3):265-71
12767474
Chem Biol. 2008 Jul 21;15(7):683-92
18635005
Dalton Trans. 2009 Jun 21;(23):4423-5
19488435
Front Biosci. 2005 Jan 01;10:275-87
15574368
Phys Chem Chem Phys. 2010 Jul 14;12(26):7266-75
20490399
Biochemistry. 2006 May 2;45(17):5468-77
16634628
Chemistry. 2011 Apr 11;17(16):4619-25
21322072
Viruses. 2010 Feb;2(2):503-31
21994646
J Biol Chem. 1991 Dec 25;266(36):24359-66
1761538
Ann N Y Acad Sci. 1967 Mar 15;141(1):300-1
5232241
Phys Rev Lett. 2006 Mar 17;96(10):107202
16605785
J Am Chem Soc. 2008 Apr 2;130(13):4553-61
18331042
Eur J Med Chem. 2008 Sep;43(9):1963-70
18342405
Chem Pharm Bull (Tokyo). 1992 Mar;40(3):805-7
1377101
Chem Rev. 2010 Oct 13;110(10):6009-48
20666374
Chem Soc Rev. 2007 Jan;36(1):105-21
17173149
Antiviral Res. 1996 Nov;32(3):141-8
8955509
Chem Rev. 1998 Feb 5;98(1):327-358
11851509
J Biol Chem. 1993 Jun 5;268(16):11939-45
8505318
Pharmacol Res. 2002 Oct;46(4):357-61
12361699
Antimicrob Agents Chemother. 1988 Sep;32(9):1300-3
3058016
Angew Chem Int Ed Engl. 2009;48(11):2035-8
19189361
Ann N Y Acad Sci. 1967 Mar 15;141(1):291-9
5342258
Biomed Pharmacother. 2006 Jun;60(5):211-9
16737794
Antiviral Res. 1991 Feb;15(2):113-24
1859202
Biochim Biophys Acta. 1965 Jul 29;105(1):193-5
4221326
Anticancer Drugs. 2005 Jan;16(1):101-6
15613912
Dalton Trans. 2010 Jan 7;(1):21-36
20023927
Biol Pharm Bull. 1995 Jul;18(7):996-1000
7581257
Exp Mol Pathol. 1990 Dec;53(3):255-64
2257932
Antimicrob Agents Chemother. 1997 Jul;41(7):1423-7
9210659