Peptidomimetics – A Versatile Route to Biologically Active Compounds

Abstract

Proteins are vital for basically every known organism. Therefore the investigation of their structure, the development of a deeper understanding of protein-protein interactions and the design of novel peptides, which selectively interact with proteins are fields of active research. Small peptides consisting of the 20 natural amino acids typically show high conformational flexibility and a low in-vivo stability which hampers their application as tools in medicinal diagnostics or molecular biology. One very versatile strategy to overcome such drawbacks is the use of peptidomimetics. These are small

Synthesis of gem-diamino acid derivatives by a Hofmann rearrangement

“…Their structure was derived from natural peptides and they should have the ability to bind to their natural targets in the same way as the natural sequences and hence should produce similar biological effects. It is possible to design these molecules in such a way that they show similar biological effects as their peptide role models but with enhanced properties like a higher proteolytic stability, higher bioavailability and also often with improved selectivity or potency (Grauer and König 2009;Liskamp et al 2011;Deshmukh and Purohit 2012). In the field of peptidomimetic synthesis, many efforts have been devoted to design and obtain retro-peptidic structures that are characterized by two inversion points of a natural peptide sequence, namely a malonyl residue and a gem-diaminic residue.…”

Dye‐Labeled Cα‐Tetrasubstituted α‐Amino Acids

“…After separation by column chromatography, 18a was coupled with 5 under phase-transfer conditions using Pd(OAc) 2 in the presence of Na 2 CO 3 and Bu 4 NBr as phase-transfer catalyst. Product 18c was obtained in a moderate yield of 57%.…”

“…In this context, the major drawback of small natural peptides is the conformational flexibility as well as the biological and chemical instability, which may hamper the investigation of biological processes or to perform structural studies. Therefore, the rational design and synthesis of peptides and peptidomimetics [4] [5] with defined structural properties [6] [7] attracted interest of chemists and biologists in the recent past. To stabilize or mimic the conformation of peptides, many different approaches were followed [8].…”

Addressing Protein–Protein Interactions with Small Molecules: A Pro‐Pro Dipeptide Mimic with a PPII Helix Conformation as a Module for the Synthesis of PRD‐Binding Ligands

“…The required dipeptide intermediate A would in turn be derived from appropriately protected vinylproline building blocks B and C; the synthesis of these is however not trivial. [13,14] As building block B, the Boc-protected trans-3-vinylproline 6 was synthesized starting from l-pyroglutamic acid (1) by the sequence shown in Scheme 2. [15] First, conversion of the carboxylic acid into a TPS-protected alcohol followed by NBoc protection afforded 2, which was subsequently transformed to the a,b-unsaturated derivative 3 through aselenylation and oxidation-induced elimination using ozone.…”