[Association of skin problems with coat colour and white markings in three-year-old horses of the Franches-Montagnes breed]. / Assoziation zwischen Hautgesundheit und Fellfarbe sowie weissen Abzeichen bei dreijährigen Freibergerpferden.

In the last 30 years the amount of white markings in the population of Franches-Montagnes horses (FM) has more than doubled which has led to some controversy, particularly in respect to the health of the horses. The objective of this study was to investigate if the coat colour and white markings have an impact on selected skin diseases and hoof horn abnormalities. To this purpose 974 three-year-old FM were subjected to a clinical examination during the field and station tests organized by the FM breeding association. In 16.9% of the horses, one or several equine sarcoids were detected, 15.2% of the horses showed clinical signs of pastern dermatitis, 1.1% of insect bite hypersensitivity and 18.0% of dermatitis of other aetiology. Abnormalities of the hoof horn were found in 20.1% of the horses. The prevalence of pastern dermatitis was 2.6 times higher in legs with white markings than in legs with pigmented skin (p <0.0001). The probability ofsuffering from sunburn and hoof horn of lesser quality was increased in animals with an elevated white marking index (WAI; p = 0.022 and p = 0.038), on the other hand, horses with sarcoids had a significantly lower WAI than sound horses (p = 0.038). Our study shows that FM horses with more pronounced white markings have an increased risk to suffer from pastern dermatitis, sunburns and hoof horn abnormalities. The coat colour was not associated with skin diseases.

High-throughput organic synthesis of peptide mimetics.

This article is a subjective review of the literature from 1999 to March 2001. It seeks to highlight current progress in the high-throughput synthesis of peptide mimetics. The review is loosely classified into sections based on the type of secondary structural feature which is being mimicked (reverse turn, beta-strand, peptide surrogates) or a common motif. The examples chosen have demonstrated the ability to produce a large number of compounds rapidly or, in our opinion, the method could produce large numbers of compounds if desired.

Lead compounds discovered from libraries.

Lead compounds with the potential to progress to viable drug candidates have been identified from libraries using several strategies. These include rapid screening of large diverse collections, thematic libraries, project-directed libraries, and three-dimensional molecular models of corporate databases. There have been numerous success stories, including the identification of several clinical candidates.

Solid-supported synthesis of a peptide beta-turn mimetic.

[structure: see text]The solid-supported synthesis of a bicyclic diketopiperazine, a potential peptide beta-turn mimetic, is described. The Ugi reaction between the resin ester of alpha-N-Boc-diaminopropionic acid (an amine input), alpha-bromo acid, aldehyde, and isocyanide is the key step in the proposed protocol.

Automated high-throughput liquid-liquid extraction for initial purification of combinatorial libraries.

An automated high-throughput liquid-liquid extraction (LLE) methodology has been developed and utilized for the initial purification of the combinatorial library samples containing unreacted amines and other water-soluble byproducts or impurities. Various extraction solvents were evaluated along with different extraction devices. The LLE method was automated using 96-well-format plates and a robotic liquid-handling workstation. In the optimized LLE method, crude combinatorial library samples were dissolved in a water-immiscible organic solvent, butyl acetate, and added to each well in a 96-well-format plate packed with an inert support material coated with hydrochloric acid. Separation occurs based on the partitioning of the compounds between two liquid phases. Product recovery, purity, and amine removal efficiency were determined by HPLC with and without precolumn derivatization. The automated method was successfully applied to the cleanup of some representative combinatorial library samples with greater than 98% amine removal and an average product purity of 90%. The application of the automated high-throughput LLE method should greatly reduce the labor, time, and cost associated with the purification of combinatorial libraries.