edoc

Nanomolar E-selectin antagonists with prolonged half-lives by a fragment-based approach.

Egger, Jonas and Weckerle, Céline and Cutting, Brian and Schwardt, Oliver and Rabbani, Said and Lemme, Katrin and Ernst, Beat. (2013) Nanomolar E-selectin antagonists with prolonged half-lives by a fragment-based approach. Journal of the American Chemical Society, 135 (26). pp. 9820-9828.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A6211899

Downloads: Statistics Overview

Abstract

Selectins, a family of C-type lectins, play a key role in inflammatory diseases (e.g., asthma and arthritis). However, the only millimolar affinity of sialyl Lewis(x) (sLe(x)), which is the common tetrasaccharide epitope of all physiological selectin ligands, has been a major obstacle to the development of selectin antagonists for therapeutic applications. In a fragment-based approach guided by NMR, ligands binding to a second site in close proximity to a sLe(x) mimic were identified. A library of antagonists obtained by connecting the sLe(x) mimic to the best second-site ligand via triazole linkers of different lengths was evaluated by surface plasmon resonance. Detailed analysis of the five most promising candidates revealed antagonists with K(D) values ranging from 30 to 89 nM. In contrast to carbohydrate-lectin complexes with typical half-lives (t(1/2)) in the range of one second or even less, these fragment-based selectin antagonists show t1/2 of several minutes. They exhibit a promising starting point for the development of novel anti-inflammatory drugs.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molekulare Pharmazie (Ernst)
UniBasel Contributors:Ernst, Beat and Weckerle, Celine and Egger, Jonas and Cutting, Brian and Schwardt, Oliver and Rabbani, Said
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:American Chemical Society
ISSN:0002-7863
e-ISSN:1520-5126
Note:Publication type according to Uni Basel Research Database: Journal article
Related URLs:
Identification Number:
Last Modified:23 Nov 2017 08:17
Deposited On:31 Jan 2014 09:49

Repository Staff Only: item control page