A multi-state model analysis of the time from ethical approval to publication of clinical research studies.

Background: Results of medical research should be made publicly available in a timely manner to enable patients and health professionals to make informed decisions about health issues. We aimed to apply a multi-state model to analyze the overall time needed to publish study results, and to examine predictors of the timing of transitions within the research process from study initiation through completion/discontinuation to eventual publication.

Methods: Using a newly developed multi-state model approach, we analysed the effect of different study-related factors on each of the transitions from study approval to eventual publication, using a data set of clinical studies approved by a German research ethics committee between 2000 and 2002.

Asymmetric synthesis and affinity of potent sialyltransferase inhibitors based on transition-state analogues.

Inhibitors that are structurally related to the transition-state model of the proposed SN1-type mechanism of sialyl transfer, exhibit particularly high binding affinities to alpha(2-6)sialyltransferases. Furthermore, replacing the neuraminyl residue with a simple aryl or hetaryl ring and substituting the carboxylate group for a phosphonate moiety, improves both binding affinity and synthetic accessibility. Herein we report on the synthesis and inhibition of a wide range of novel, potent transition-state analogue based alpha(2-6)sialyltransferase inhibitors comprising a planar anomeric carbon, an increased distance between the anomeric carbon and the CMP leaving group, and at least two negative charges.

Synthesis of an S-linked glycopeptide analog derived from human Tamm-Horsfall glycoprotein.

Direct base catalyzed S-glycosylation of a cysteine and a homocysteine containing peptide with O-acetyl protected bromides in DMF-water solution furnished two glycopeptide fragments. The two glycopeptide fragments were linked to the target glycopeptide with two S-glycosyl residues mimicking a part of Tamm-Horsfall glycoprotein.