Prepromelittin-related peptide

The development of solid phase peptide synthesis has released tremendous opportunities for using synthetic peptides in medicinal applications. In the last decades, peptide therapeutics became an emerging market in pharmaceutical industry. The need for synthetic strategies in order to improve peptidic properties, such as longer half-life, higher bioavailability, increased potency and efficiency is accordingly rising. In this mini-review, we present a toolbox of modifications in peptide chemistry for overcoming the main drawbacks during the transition from natural peptides to peptide therapeutics. Modifications at the level of the peptide backbone, amino acid side chains and higher orders of structures are described. Furthermore, we are discussing the future of peptide therapeutics development and their impact on the pharmaceutical market.

Coacervates are condensed liquid-like droplets formed by liquid-liquid phase separation of molecules through multiple weak associative interactions. In recent years it has emerged that not only long polymers, but also short peptides are capable of forming simple and complex coacervates. The coacervate droplets they form act as compartments that sequester and concentrate a wide range of solutes, and their spontaneous formation make coacervates attractive protocell models. The main advantage of peptides as building blocks lies in the functional diversity of the amino acid residues, which allows for tailoring of the peptide's phase separation propensity, their selectivity in guest molecule uptake and the physicochemical and catalytic properties of the compartments. The aim of this tutorial review is to illustrate the recent developments in the field of peptide-based coacervates in a systematic way and to deduce the basic requirements for both simple and complex coacervation of peptides. We review a selection of peptide coacervates that illustrates the essentials of phase separation, the limitations, and the properties that make peptide coacervates biomimetic protocells. Finally, we provide some perspectives of this novel research field in the direction of active droplets, moving away from thermodynamic equilibrium.

Pharmaceutical and biotechnological research sorts protein drug delivery systems by importance based on their various therapeutic applications. The effective and potent action of the proteins/peptides makes them the drugs of choice for the treatment of numerous diseases. Major research issues in protein delivery include the stabilization of proteins in delivery devices and the design of appropriate target-specific protein carriers. Many efforts have been made for effective delivery of proteins/peptidal drugs through various routes of administrations for successful therapeutic effects. Nanoparticles made of biodegradable polymers such as poly lactic acid, polycaprolactone, poly(lactic-co-glycolic acid), the poly(fumaric-co-sebacic) anhydride chitosan, and modified chitosan, as well as solid lipids, have shown great potential in the delivery of proteins/peptidal drugs. Moreover, scientists also have used liposomes, PEGylated liposomes, niosomes, and aquasomes, among others, for peptidal drug delivery. They also have developed hydrogels and transdermal drug delivery systems for peptidal drug delivery. A receptor-mediated delivery system is another attractive strategy to overcome the limitation in drug absorption that enables the transcytosis of the protein across the epithelial barrier. Modification such as PEGnology is applied to various proteins and peptides of the desired protein and peptides also increases the circulating life, solubility and stability, pharmacokinetic properties, and antigenicity of protein. This review focuses on various approaches for effective protein/peptidal drug delivery, with special emphasis on insulin delivery.