Making protein interactions druggable: Targeting PDZ domains

被引:164
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
    Aarts, M
    Liu, YT
    Liu, LD
    Besshoh, S
    Arundine, M
    Gurd, JW
    Wang, YT
    Salter, MW
    Tymianski, M
    [J]. SCIENCE, 2002, 298 (5594) : 846 - 850
  • [2] Small-molecule inhibitors of protein-protein interactions: Progressing towards the dream
    Arkin, MR
    Wells, JA
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (04) : 301 - 317
  • [3] Ionotropic glutamate receptor biology: Effect on synaptic connectivity and function in neurological disease
    Barnes, GN
    Slevin, JT
    [J]. 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
    Baron, A
    Deval, E
    Salinas, M
    Lingueglia, E
    Voilley, N
    Lazdunski, M
    [J]. 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
    Beneyto, M
    Meador-Woodruff, JH
    [J]. 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
    Bengel, D
    Murphy, DL
    Andrews, AM
    Wichems, CH
    Feltner, D
    Heils, A
    Mössner, R
    Westphal, H
    Lesch, KP
    [J]. MOLECULAR PHARMACOLOGY, 1998, 53 (04) : 649 - 655
  • [7] Modulation of protein-protein interactions with small organic molecules
    Berg, T
    [J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (22) : 2462 - 2481
  • [8] Classification of PDZ domains
    Bezprozvanny, I
    Maximov, A
    [J]. 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
    Bjerggaard, C
    Fog, JU
    Hastrup, H
    Madsen, K
    Loland, CJ
    Javitch, JA
    Gether, U
    [J]. JOURNAL OF NEUROSCIENCE, 2004, 24 (31) : 7024 - 7036
  • [10] Epidermolysis bullosa and embryonic lethality in mice lacking the multi-PDZ domain protein GRIP1
    Bladt, F
    Tafuri, A
    Gelkop, S
    Langille, L
    Pawson, T
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (10) : 6816 - 6821