19245-87-5Relevant articles and documents
Conjugation of Short Peptides to Dibenzodiazepinone-Type Muscarinic Acetylcholine Receptor Ligands Determines M2R Selectivity
Pegoli, Andrea,Wifling, David,Gruber, Corinna G.,She, Xueke,Hübner, Harald,Bernhardt, Günther,Gmeiner, Peter,Keller, Max
, p. 5358 - 5369 (2019)
Muscarinic acetylcholine receptors (MRs), comprising five subtypes (M1R-M5R) in humans, exhibit a high degree of structural similarity. Therefore, subtype-selective MR agonists and antagonists are lacking. We present an approach to highly M2R-selective MR antagonists based on the conjugation of di- or tripeptides to M2R-preferring dibenzodiazepinone-type MR antagonists. M2R selectivity was dependent on the peptide sequence and on the type of linker. The introduction of basic amino acids resulted in improved M2R selectivity (e.g., UR-AP148 (48): pKi (hM2R) of 8.97, ratio of Ki M1R/M2R/M3R/M4R/M5R of 49:1:6500:60:400) compared to reported pyridobenzo- and dibenzodiazepinone-type MR ligands. A supposed dualsteric binding mode of the DIBA-peptide conjugates, such as 48, at MRs was supported by molecular dynamics simulations.
The dimethylsulfoxonium methylide as unique reagent for the simultaneous deprotection of amino and carboxyl function of N-Fmoc-α-amino acid and N-Fmoc-peptide esters
Spinella, Mariagiovanna,De Marco, Rosaria,Belsito, Emilia L.,Leggio, Antonella,Liguori, Angelo
, p. 2010 - 2016 (2013/03/13)
The dimethylsulfoxonium methylide is described as a unique and useful reagent for the simultaneous deprotection of amino and carboxyl function of N-Fmoc-α-amino acid and N-Fmoc-peptide esters. The new methodology was applied successfully both to solution- and solid-phase peptide synthesis. The adopted methodology was extended successfully also to peptides containing amino acids bearing acid-sensitive protecting group in side chains. Furthermore no measurable epimerization was observed in the deprotection reaction of N-Fmoc-dipeptide methyl esters with dimethylsulfoxonium methylide.
Thermitase - A Thermostable Serine Protease. II. Synthesis of Substrate Analogous Peptide Chloromethyl Ketones as Irreversibly Acting Inhibitors
Jahreis, Guenther,Smalla, Kornelia,Fittkau, Siegfried
, p. 41 - 47 (2007/10/02)
The preparation of dipeptide to pentapeptide chloromethyl ketones of alanine with variation of the amino acid in the P1 and P2 position of the peptides is described.The synthesis is performed by fragment condensation of N-acylated amino acids or peptides with the unprotected chloromethyl ketone derivatives of amino acids and peptides, respectively.Some examples of enzyme inactivation by peptide chloromethyl ketones are discussed.