N-methylation in amino acids and peptides: Scope and limitations.

Active pharmaceutical ingredients (APIs) can be divided into two types, namely chemical and biological entities. Traditionally, the former has been associated with the so-called small molecules. The revival of peptides in pharmaceutical industry results from their importance in many biological roles.

Solid-Phase Synthesis of Pyrrole Derivatives through a Multicomponent Reaction Involving Lys-Containing Peptides.

The synthesis of pyrroles has received considerable attention because of their biological and pharmaceutical activities. Herein we describe a solid-phase multicomponent reaction that utilizes Lys as a N donor, β-nitrostyrenes, 1,3-dicarbonyl compounds, and FeCl as an easily accessible catalyst under microwave irradiation to afford the subsequent pyrrole derivatives in high conversions. The strategy combines three of the most powerful tools in modern synthetic chemistry: the solid-phase mode, microwave activation, and a multicomponent reaction.

Teixobactin as a scaffold for unlimited new antimicrobial peptides: SAR study.

It looks that a new era of antimicrobial peptides (AMPs) started with the discovery of teixobactin, which is a "head to side-chain" cyclodepsipeptide. It was isolated from a soil gram-negative b-proteobacteria by means of a revolutionary technique. Since there, several groups have developed synthetic strategies for efficient synthesis of this peptide and its analogues as well.

Re-evaluating the stability of COMU in different solvents.

COMU is uronium-type coupling reagent based on OxymaPure. It showed several advantages over classical benzotriazole-based coupling reagents such as higher solubility, water-soluble byproduct, and monitoring the reaction by changing of color. Although COMU is well known to perform excellent in solution, but its hydrolytic stability in DMF limits its use in automatic peptide synthesizer.

Lysine Scanning of Arg-Teixobactin: Deciphering the Role of Hydrophobic and Hydrophilic Residues.

Teixobactin is a recently discovered antimicrobial cyclodepsipeptide with good activity against Gram positive bacteria. Taking Arg-teixobactin as a reference, where the nonproteinogenic residue l-allo-enduracididine was substituted by arginine, a lysine scan was performed to identify the importance of keeping the balance between hydrophilic and hydrophobic amino acids for the antimicrobial activities of this peptide family. Thus, the substitution of four isoleucine residues present in the natural sequence by lysine led to a total loss of activity.

Synthesis and Biological Evaluation of a Teixobactin Analogue.

The first synthesis and biological activity of a teixobactin analogue is reported. Substitution of the unusual L-allo-enduracididine residue by the naturally occurring L-arginine was achieved, and the analogue gave an activity trend similar to that of teixobactin (against Gram-postive bacteria) and meropenem, which was approved by the FDA in 1996. The synthetic route used allows for the synthesis of the natural product as well as the development of a program of medicinal chemistry.

2-Methyltetrahydrofuran and cyclopentyl methyl ether for green solid-phase peptide synthesis.

2-MeTHF and CPME were evaluated as greener alternatives for the most employed solvents in peptide synthesis. The ability of these solvents to dissolve amino acid derivatives and a range of coupling reagents were evaluated as well as the swelling of polystyrene and polyethylene glycol resins. In addition, racemization and coupling efficiencies were also determined.

Peptide synthesis beyond DMF: THF and ACN as excellent and friendlier alternatives.

To date, DMF has been considered as the only solvent suitable for peptide synthesis. Here we demonstrate the capacity of THF and ACN, which are friendlier solvents than DMF, to yield the product in higher purity than DMF. Using various peptide models, both THF and ACN reduced racemization in solution-phase and solid-phase synthesis when compared with DMF.

TOMBU and COMBU as Novel Uronium-type peptide coupling reagents derived from Oxyma-B.

Here we describe two novel uronium salts, TOMBU and COMBU, derived from the recently described Oxyma-B for use in peptide bond synthesis. These coupling reagents are more stable than COMU in DMF. Furthermore, using various peptide synthetic models in solution and solid-phase synthesis, we reveal that they show better performance than HBTU in terms of preserving chiral integrity and coupling yields, but slightly worse performance than COMU.

Oxyma-B, an excellent racemization suppressor for peptide synthesis.

Peptide-bond formation is a key process in the synthesis of peptide oligomers. Among the many coupling techniques reported, carbodiimides combine strong acylation potency and smooth reaction conditions and are commonly used in the presence of additives. Recently, ethyl 2-cyano-2-(hydroxyimino)acetate (OxymaPure) has emerged as a highly reactive alternative to the classic and explosion-prone benzotriazolic additives, namely 1-hydroxybenzotriazole (HOBt) and 1-hydroxy-7-azabenzotriazole (HOAt).