Highly chemoselective ligation of thiol- and amino-peptides on a bromomaleimide core.

Application of a bromomaleimide core allows for the incorporation of three different peptides. The key reactions of the process are the selective stapling of both thiol- and amino-peptides on two different sites of the core. The thiol-peptide attacks and replaces the bromide whereas the amino-peptide attaches to the ene-position of the core revealing differential and selective reactivity. This platform will have further application in protein chemistry, multidrug presentation and vaccine preparation.

Chemical Platforms for Peptide Vaccine Constructs.

Knowledge of the sequences and structures of proteins from pathogenic microorganisms has been put to great use in the field of protein chemistry for the development of peptide-based vaccines. These vaccine constructs include chemically tailored, shorter peptidic fragments that can induce high immunogenicity, thus shunning the allergenic and nonimmunogenic part of the antigens. Based on this concept, several different chemistries have been pursued to obtain novel platforms onto which antigenic epitopes can be tethered, with the aim to achieve a higher antibody response. In this regard, here we attempt to summarize the chemical strategies developed for the presentation of peptide epitopes.

An efficient solid-phase strategy for total synthesis of naturally occurring amphiphilic marine siderophores: amphibactin-T and moanachelin ala-B.

Microorganisms such as bacteria, fungi and some plants secrete an abundance of suites of low molecular weight, high-affinity iron(iii)-chelating acylated siderophores. The peptide composition of a suite of amphiphilic siderophores generated by a Vibrio species, isolated from oligotrophic open ocean water, contained the same iron(iii)-scavenging polar head group and is attached to a fatty acid. In the present study, we report the first total synthesis of the naturally obtainable marine siderophores amphibactin-T and moanachelin ala-B on solid-phase using standard Fmoc-chemistry. Furthermore, we discuss the preparation of orthogonal protected Orn amino acid 'N(α)-Fmoc-N(δ)-(acetyl)-N(δ)-(benzoyloxy)-ornithine' [Fmoc-Orn(Ac,OBz)-OH], which is the most important constructive building block for amphibactin and moanachelin siderophores syntheses. The applications of this Orn unit on solid-phase have also been discussed.

6-(Bromomaleimido)hexanoic acid as a connector for the construction of multiple branched peptide platforms.

We report on a novel and user-friendly platform based on a bromomaleimide moiety to obtain branched peptides. The platform is stable for all SPPS conditions. The bromomaleimide core was conjugated to n-copies of thiol-peptide in-solution to obtain two/four/eight-armed dendrimers. Using 'n' number of bromomaleimide analogues, 2(n) ligands were incorporated at both bromo and ene positions via a thioether bond. This method has the advantage of high conversion in a short time, thus enabling effortless purification and characterization processes.

Immobilized coupling reagents: synthesis of amides/peptides.

The primary idea of using immobilized reagents in organic synthetic chemistry is to simplify the downstream process, product workup and isolation, and therefore avoiding time-consuming and expensive chromatographic separations, which are intrinsic to every synthetic process. Numerous polymer-bounded reagents are commercially available and applicable to almost all kinds of synthetic chemistry conversions. Herein, we have covered all known supported-coupling reagents and bases which have had a great impact in amide/peptide bond formation. These coupling reagents have been used for the activation of a carboxyl moiety; thus generating an active acylating species that is ready to couple with an amine nucleophile liberating the amide/peptide and polymeric support which can be regenerated for reuse. This also addresses a large variety of anchored coupling reagents, additives, and bases that have only been employed in amide/peptide syntheses during the last six decades.

Microreactors for peptide synthesis: looking through the eyes of twenty first century !!!

The twenty first century has witnessed several advances in synthetic chemistry, among them microreactors. It is expected that these devices will have a considerable impact on synthetic organic chemistry since they offer a wide range of applications in various fields. Perhaps the synthesis of peptides deserves mention in this regard as these molecules are emerging as therapeutics and offer several advantages over the so-called small molecules. This minireview does not aim to address microreactors in detail, but explains various peptide synthesis methods that involve microfluidic techniques, highlighting the need for further improvement and expansion of microdevices/microreactors.

Solid-phase peptide synthesis (SPPS), C-terminal vs. side-chain anchoring: a reality or a myth.

Here we review the strategies for the solid-phase synthesis of peptides starting from the side chain of the C-terminal amino acid. Furthermore, we provide experimental data to support that C-terminal and side-chain syntheses give similar results in terms of purity. However, the stability of the two bonds that anchor the peptide to the polymer may determine the overall yield and this should be considered for the large-scale production of peptides. In addition, resins/linkers which do not subject to side reactions can be preferred for some peptides.