English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Rational design of cyclic peptide inhibitors of U2AF homology motif (UHM) domains to modulate pre-mRNA splicing.

Jagtap, P. K. A., Garg, D., Kapp, T. G., Will, C. L., Demme, O., Lührmann, R., et al. (2016). Rational design of cyclic peptide inhibitors of U2AF homology motif (UHM) domains to modulate pre-mRNA splicing. Journal of Medicinal Chemistry, 59(22), 10190-10197. doi:10.1021/acs.jmedchem.6b01118.

Item is

Files

show Files
hide Files
:
2354728.pdf (Publisher version), 3MB
 
File Permalink:
-
Name:
2354728.pdf
Description:
-
OA-Status:
Visibility:
Restricted (UNKNOWN id 303; )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
2354728_Suppl.6b01118 (Supplementary material), 145KB
Name:
2354728_Suppl.6b01118
Description:
-
OA-Status:
Visibility:
Public
MIME-Type / Checksum:
text/html / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Jagtap, P. K. A., Author
Garg, D., Author
Kapp, T. G., Author
Will, C. L.1, Author           
Demme, O., Author
Lührmann, R.1, Author           
Kessler, H., Author
Sattler, M., Author
Affiliations:
1Department of Cellular Biochemistry, MPI for biophysical chemistry, Max Planck Society, ou_578576              

Content

show
hide
Free keywords: -
 Abstract: U2AF homology motifs (UHMs) are atypical RNA recognition motif domains that mediate critical protein–protein interactions during the regulation of alternative pre-mRNA splicing and other processes. The recognition of UHM domains by UHM ligand motif (ULM) peptide sequences plays important roles during early steps of spliceosome assembly. Splicing factor 45 kDa (SPF45) is an alternative splicing factor implicated in breast and lung cancers, and splicing regulation of apoptosis-linked pre-mRNAs by SPF45 was shown to depend on interactions between its UHM domain and ULM motifs in constitutive splicing factors. We have developed cyclic peptide inhibitors that target UHM domains. By screening a focused library of linear and cyclic peptides and performing structure–activity relationship analysis, we designed cyclic peptides with 4-fold improved binding affinity for the SPF45 UHM domain compared to native ULM ligands and 270-fold selectivity to discriminate UHM domains from alternative and constitutive splicing factors. These inhibitors are useful tools to modulate and dissect mechanisms of alternative splicing regulation.

Details

show
hide
Language(s): eng - English
 Dates: 2016-10-182016
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1021/acs.jmedchem.6b01118
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Journal of Medicinal Chemistry
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 59 (22) Sequence Number: - Start / End Page: 10190 - 10197 Identifier: -