Making protein interactions druggable: Targeting PDZ domains

被引:165
作者
Dev, KK [1 ]
机构
[1] Novartis Pharma AG, Neurosci Res, Novartis Inst Biomed Res, CH-4002 Basel, Switzerland
关键词
D O I
10.1038/nrd1578
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Modulating protein-protein interactions involved in disease pathways is an attractive strategy for developing drugs, but remains a challenge to achieve. One approach is to target certain domains within proteins that mediate these interactions. One example of such a domain is the PDZ domain, which is involved in interactions between many different proteins in a variety of cellular contexts. Because PDZ domains have well-defined binding sites, they are promising targets for drug discovery. However, there is still much to learn about the function of these domains before drugs targeting PDZ interactions can become a reality.
引用
收藏
页码:1047 / 1056
页数:10
相关论文
共 107 条
[1]   Treatment of ischemic brain damage by perturbing NMDA receptor-PSD-95 protein interactions [J].
Aarts, M ;
Liu, YT ;
Liu, LD ;
Besshoh, S ;
Arundine, M ;
Gurd, JW ;
Wang, YT ;
Salter, MW ;
Tymianski, M .
SCIENCE, 2002, 298 (5594) :846-850
[2]   Small-molecule inhibitors of protein-protein interactions: Progressing towards the dream [J].
Arkin, MR ;
Wells, JA .
NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (04) :301-317
[3]   Ionotropic glutamate receptor biology: Effect on synaptic connectivity and function in neurological disease [J].
Barnes, GN ;
Slevin, JT .
CURRENT MEDICINAL CHEMISTRY, 2003, 10 (20) :2059-2072
[4]   Protein kinase C stimulates the acid-sensing ion channel ASIC2a via the PDZ domain-containing protein PICK1 [J].
Baron, A ;
Deval, E ;
Salinas, M ;
Lingueglia, E ;
Voilley, N ;
Lazdunski, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (52) :50463-50468
[5]   Expression of transcripts encoding AMPA receptor subunits and associated postsynaptic proteins in the macaque brain [J].
Beneyto, M ;
Meador-Woodruff, JH .
JOURNAL OF COMPARATIVE NEUROLOGY, 2004, 468 (04) :530-554
[6]   Altered brain serotonin homeostasis and locomotor insensitivity to 3,4-methylenedioxymethamphetamine ("ecstasy") in serotonin transporter-deficient mice [J].
Bengel, D ;
Murphy, DL ;
Andrews, AM ;
Wichems, CH ;
Feltner, D ;
Heils, A ;
Mössner, R ;
Westphal, H ;
Lesch, KP .
MOLECULAR PHARMACOLOGY, 1998, 53 (04) :649-655
[7]   Modulation of protein-protein interactions with small organic molecules [J].
Berg, T .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (22) :2462-2481
[8]   Classification of PDZ domains [J].
Bezprozvanny, I ;
Maximov, A .
FEBS LETTERS, 2001, 509 (03) :457-462
[9]   Surface targeting of the dopamine transporter involves discrete epitopes in the distal C terminus but does not require canonical PDZ domain interactions [J].
Bjerggaard, C ;
Fog, JU ;
Hastrup, H ;
Madsen, K ;
Loland, CJ ;
Javitch, JA ;
Gether, U .
JOURNAL OF NEUROSCIENCE, 2004, 24 (31) :7024-7036
[10]   Epidermolysis bullosa and embryonic lethality in mice lacking the multi-PDZ domain protein GRIP1 [J].
Bladt, F ;
Tafuri, A ;
Gelkop, S ;
Langille, L ;
Pawson, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (10) :6816-6821