Metoda O-acyloizopeptydowa w syntezie peptydow

Proteins are macromolecules that carry out most of the biochemical functions of the cell, which strongly depend on the secondary and tertiary structure, defined by the amino acid sequence of a polypeptide chain. The importance of peptides and proteins in biology and medicine inspired chemists to develop strategies for their synthesis. The main limitation to the preparation of long peptides is their tendency to aggregation, what makes the coupling and deprotection reaction ineffective, and purification of the compounds difficult. Inter- and intramolecular interactions, hydrophobic character, the presence of multiple hydrogen bonds significantly affect the secondary structure of peptides, making further extension of the peptide chain very difficult. Undesirable aggregation process may be disrupted by reduction of hydrophobic interactions. For this purpose, various methods are used, based on the implementation of specific modifications to the peptide chain, affecting its secondary structure. These methods include, for example, incorporation of pseudoproline building blocks [5] and proximity induced peptide ligation [6, 7]. In some cases, it is convenient to extend the amino acid side chain to form isopeptides (Fig. 1) [14–16]. Depsipeptides can be created with the natural amino acids such as cysteine, serine, threonine, tyrosine, or tryptophan. The basic requirement is the presence of β-hydroxyamino component. The presence of a depsipeptide moiety in place of an amide bond significantly change the secondary structure of native peptide and prevents from aggregation, leading to higher yields of desired compounds [18]. In the solution phase peptide synthesis, this method is free from racemization [19]. Isodipeptide units can be successfully applied in SPPS for the synthesis of “difficult sequence”-containing peptides [19]. In this paper, many examples of effective use of O-acylisopeptides method in peptide synthesis are discussed.