Drugs for 'protein clouds': Targeting intrinsically disordered transcription factors

A. Dunker, Vladimir N. Uversky

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Transcription factors (TFs) are very attractive but difficult drug targets. The difficulties come from several directions including the binding promiscuity of TFs and the intrinsically disordered nature of their binding sites, which often resemble 'protein clouds'. For a long time the targeting of proteins without defined structures was considered infeasible. Data have now emerged showing that selective blocking of specific interactions of intrinsically disordered TFs with their protein binding partners is possible. Initial hits have been optimized to increase their specificity and affinity. Several strategies have been elaborated for elucidating the mechanisms of blocking of intrinsic disorder-based protein-protein interactions. However, challenges remain in the field of drug development for 'protein clouds'; such development is still in its earliest stage.

Original languageEnglish
Pages (from-to)782-788
Number of pages7
JournalCurrent Opinion in Pharmacology
Volume10
Issue number6
DOIs
StatePublished - Dec 2010

Fingerprint

Protein Transport
Transcription Factors
Pharmaceutical Preparations
Proteins
Protein Binding
Binding Sites

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

Cite this

Drugs for 'protein clouds' : Targeting intrinsically disordered transcription factors. / Dunker, A.; Uversky, Vladimir N.

In: Current Opinion in Pharmacology, Vol. 10, No. 6, 12.2010, p. 782-788.

Research output: Contribution to journalArticle

@article{870dbb428f7c495e9fc9304ac3f31549,
title = "Drugs for 'protein clouds': Targeting intrinsically disordered transcription factors",
abstract = "Transcription factors (TFs) are very attractive but difficult drug targets. The difficulties come from several directions including the binding promiscuity of TFs and the intrinsically disordered nature of their binding sites, which often resemble 'protein clouds'. For a long time the targeting of proteins without defined structures was considered infeasible. Data have now emerged showing that selective blocking of specific interactions of intrinsically disordered TFs with their protein binding partners is possible. Initial hits have been optimized to increase their specificity and affinity. Several strategies have been elaborated for elucidating the mechanisms of blocking of intrinsic disorder-based protein-protein interactions. However, challenges remain in the field of drug development for 'protein clouds'; such development is still in its earliest stage.",
author = "A. Dunker and Uversky, {Vladimir N.}",
year = "2010",
month = "12",
doi = "10.1016/j.coph.2010.09.005",
language = "English",
volume = "10",
pages = "782--788",
journal = "Current Opinion in Pharmacology",
issn = "1471-4892",
publisher = "Elsevier BV",
number = "6",

}

TY - JOUR

T1 - Drugs for 'protein clouds'

T2 - Targeting intrinsically disordered transcription factors

AU - Dunker, A.

AU - Uversky, Vladimir N.

PY - 2010/12

Y1 - 2010/12

N2 - Transcription factors (TFs) are very attractive but difficult drug targets. The difficulties come from several directions including the binding promiscuity of TFs and the intrinsically disordered nature of their binding sites, which often resemble 'protein clouds'. For a long time the targeting of proteins without defined structures was considered infeasible. Data have now emerged showing that selective blocking of specific interactions of intrinsically disordered TFs with their protein binding partners is possible. Initial hits have been optimized to increase their specificity and affinity. Several strategies have been elaborated for elucidating the mechanisms of blocking of intrinsic disorder-based protein-protein interactions. However, challenges remain in the field of drug development for 'protein clouds'; such development is still in its earliest stage.

AB - Transcription factors (TFs) are very attractive but difficult drug targets. The difficulties come from several directions including the binding promiscuity of TFs and the intrinsically disordered nature of their binding sites, which often resemble 'protein clouds'. For a long time the targeting of proteins without defined structures was considered infeasible. Data have now emerged showing that selective blocking of specific interactions of intrinsically disordered TFs with their protein binding partners is possible. Initial hits have been optimized to increase their specificity and affinity. Several strategies have been elaborated for elucidating the mechanisms of blocking of intrinsic disorder-based protein-protein interactions. However, challenges remain in the field of drug development for 'protein clouds'; such development is still in its earliest stage.

UR - http://www.scopus.com/inward/record.url?scp=78149497463&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78149497463&partnerID=8YFLogxK

U2 - 10.1016/j.coph.2010.09.005

DO - 10.1016/j.coph.2010.09.005

M3 - Article

C2 - 20889377

AN - SCOPUS:78149497463

VL - 10

SP - 782

EP - 788

JO - Current Opinion in Pharmacology

JF - Current Opinion in Pharmacology

SN - 1471-4892

IS - 6

ER -