C-acylations of polymeric phosphoranylidene acetates for C-terminal variation of peptide carboxylic acids.

C-Acylations of polymer-supported 2-phosphoranylidene acetates ("linker reagents") with protected amino acids yielded 2-acyl-2-phosphoranylidene acetates as flexible intermediates for the C-terminal variation of carboxylic acids: peptidyl-2,3-diketoesters, peptidyl vinyl ketones, peptidyl-2-ketoaldehydes, and 1,3-diamino-2-hydroxy-propanes were obtained as products. [reaction: see text]

The potential of P1 site alterations in peptidomimetic protease inhibitors as suggested by virtual screening and explored by the use of C-C-coupling reagents.

A synthetic concept is presented that allows the construction of peptide isostere libraries through polymer-supported C-acylation reactions. A phosphorane linker reagent is used as a carbanion equivalent; by employing MSNT as a coupling reagent, the C-acylation can be conducted without racemization. Diastereoselective reduction was effected with L-selectride.

An efficient method for the synthesis of peptide aldehyde libraries employed in the discovery of reversible SARS coronavirus main protease (SARS-CoV Mpro) inhibitors.

A method for the parallel solid-phase synthesis of peptide aldehydes has been developed. Protected amino acid aldehydes obtained by the racemization-free oxidation of amino alcohols with Dess-Martin periodinane were immobilized on threonyl resins as oxazolidines. Following Boc protection of the ring nitrogen to yield the N-protected oxazolidine linker, peptide synthesis was performed efficiently on this resin.

Differential quantitative analysis of MHC ligands by mass spectrometry using stable isotope labeling.

Currently, no method allows direct and quantitative comparison of MHC-presented peptides in pairs of samples, such as transfected and untransfected, tumorous and normal or infected and uninfected tissues or cell lines. Here we introduce two approaches that use isotopically labeled reagents to quantify by mass spectrometry the ratio of peptides from each source. The first method involves acetylation and is both fast and simple.

Oxoammonium Resins as Metal-Free, Highly Reactive, Versatile Polymeric Oxidation Reagents.

Polymer-supported oxidation of alcohols was conducted very efficiently by employing oxoammonium salts, the reactive intermediates in TEMPO oxidations (TEMPO=2,2,6,6-tetramethylpiperidinoxyl). These highly reactive salts (see scheme; X=Br, Cl) could be prepared and isolated on the polymeric support, and were used for the conversion of single compounds as well as of complex mixtures of alcohols.