eprintid: 19461
rev_number: 28
userid: 1419
dir: disk0/00/01/94/61
datestamp: 2013-08-07 15:35:04
lastmod: 2021-06-12 14:55:11
status_changed: 2013-08-07 15:35:04
type: article
metadata_visibility: show
item_issues_count: 0
eprint_status: archive
creators_name: Wang, Z
creators_name: McPherson, PA
creators_name: Raccor, BS
creators_name: Balachandran, R
creators_name: Zhu, G
creators_name: Day, BW
creators_name: Vogt, A
creators_name: Wipf, P
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creators_email: pwipf@pitt.edu
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creators_id: PWIPF
title: Structure-activity and high-content imaging analyses of novel tubulysins
ispublished: pub
divisions: sch_as_chemistry
full_text_status: public
abstract: The synthesis and biological evaluation of three tubulysin analogs provides the first structure-activity relationship in this family of potent cytotoxic myxobacteria metabolites. Most importantly, the labile N,O-acetal at N 14 is not essential for biological activity. Further, structural simplifications are possible without abolishing biological activities. The N-terminal amino acid can be replaced with N-methylsarcosine, and the configuration at the acetoxy-bearing stereocenter at C11 is important but not critical for almost all aspects of the biological profile. Our data encourage further development of these compounds as potential therapeutic agents in cancer treatment. © 2007 The Authors.
date: 2007-08-01
date_type: published
publication: Chemical Biology and Drug Design
volume: 70
number: 2
pagerange: 75 - 86
refereed: TRUE
issn: 1747-0277
id_number: 10.1111/j.1747-0285.2007.00541.x
pmid: 17683369
mesh_headings: Animals
mesh_headings: Cattle
mesh_headings: Cell Line, Tumor
mesh_headings: Depsipeptides--metabolism
mesh_headings: Glioblastoma--drug therapy
mesh_headings: HeLa Cells
mesh_headings: Humans
mesh_headings: Mitosis--drug effects
mesh_headings: Oligopeptides--chemical synthesis
mesh_headings: Oligopeptides--chemistry
mesh_headings: Oligopeptides--pharmacology
mesh_headings: Oligopeptides--therapeutic use
mesh_headings: Structure-Activity Relationship
mesh_headings: Thiazoles--chemical synthesis
mesh_headings: Thiazoles--chemistry
mesh_headings: Thiazoles--therapeutic use
mesh_headings: Tubulin--drug effects
mesh_headings: Tubulin Modulators--pharmacology
mesh_headings: Vinblastine--metabolism
chemical_names: 4-(2-(6-sec-butyl-9-isopropyl-2,8-dimethyl-4,7,13-trioxo-12-oxa-2,5,8-triazatetradecan-11-yl)thiazole-4-carboxamido)-2-methyl-5-phenylpentanoic acid
chemical_names: Depsipeptides
chemical_names: N14-desacetoxytubulysin H
chemical_names: Oligopeptides
chemical_names: Thiazoles
chemical_names: Tubulin
chemical_names: Tubulin Modulators
chemical_names: tubulysin A
chemical_names: dolastatin 10
chemical_names: Vinblastine
citation:   Wang, Z and McPherson, PA and Raccor, BS and Balachandran, R and Zhu, G and Day, BW and Vogt, A and Wipf, P  (2007) Structure-activity and high-content imaging analyses of novel tubulysins.  Chemical Biology and Drug Design, 70 (2).  75 - 86.  ISSN 1747-0277     
document_url: http://d-scholarship-dev.library.pitt.edu/19461/1/licence.txt