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The reaction conditions of the sortase-mediated ligation are examined, which can be used in the synthesis of a peptide nucleic acid-cell-penetrating peptide chimera. The newly obtained conjugates have displayed dose-dependent antisense activity.

A series of 1-hydroxy-7-azabenzotriazole (HOAt)-based coupling reagents was utilized for the cyclization reaction of all-L-pentapeptides to determine the efficiency of the reagents in increasing the reaction rate. The head-to-tail cyclization of all-L-penta- and -hexapeptides without turn-inducing amino acids was significantly improved by HOAt-derived onium and phosphonium salts. However, the reagents did not inhibit the formation of cyclodimers and C-terminal epimerization.

The use of several 1-hydroxy-7-azabenzotriazole-based onium salts in the cyclization process for thymopentin-derived pentapeptides showed azabenzotriazole-derived coupling agents to be most effective compared with traditional coupling reagents. Rapid cyclizations were observed, while monocyclic pentapeptide ring formation was favored by residual products of C-terminal D-amino acid.

Fmoc amino acid fluorides act as coupling reagents in the stepwise solid phase synthesis of peptaibols, as proved by the syntheses of saturnisporin SA III, alamethicin F30 and F50 and trichotoxin A50J. The end products possess a high degree of purity in this reaction, in which several difficulties encountered in the earlier methods of synthesis, such as chain degradation and racemization, are overcome. The assembly of C-terminal peptide alcohols through O-chlorotrityl resin is the initial step of this successful method of synthesizing peptaibols.

Solid-phase approach is used to prepare medium-sized peptides with the help of Fmoc amino acid fluorides. These fluorides have the ability to couple two sterically hindered amino acid groups. Fmoc function is stable toward the base in the active acylating agent Fmoc-Aib-F. Efficiency of this method is proved by the synthesis of different peptides having hindered Aib units.

The application of the depsipeptide technique to extremely difficult sequences is demonstrated and a serious side reaction involving diketopiperazine formation is uncovered and subsequently avoided by the appropriate use of the Bsmoc protecting group. The method is modified in order to allow the completely automated syntheses of long-chain depsipeptides without the need for any interruption by manual esterification procedures and the method's efficiency is comparable to that of the well-known pseudoproline method.

The formation protective systems for carboxyl and amide is described. The protective groups were derived from a secondary system incorporating two alpha-cyclopropyl units or a tertiary system having one cyclopropyl and two methyl residues. The results showed that the dicyclopropylmethyl group can be used for protecting carboxylic acid where selective removal is required in the presence of tert-butyl-derived or N-trityl side chain protection.