Synthesis of the Novel Covalent Cysteine Proteases Inhibitor with Iodoacetic Functional Group

This work presents the synthesis of the novel covalent inhibitor of cysteine proteases where epoxide has been replaced by the iodoacetyl functional group. The molecule, similar in action to E-64 and DCG-04, the commonly applied inhibitors, is additionally biotinylated and contains tyrosyl iodination sites. The Fmoc solid phase synthesis has been applied. Conjugation of iodoacetic acid with the peptide was optimized by testing different conjugation agents. The purity of the final product was verified by mass spectrometry and its bioactivity was tested by incubation with a model cysteine protease—staphopain C. Finally, it was shown that the synthesized inhibitor binds to the protein at the ratio of 1:1. More detailed analysis by means of tandem mass spectrometry proved that the inhibitor binds to the cysteine present in the active site of the enzyme.

Fmoc solid-phase synthesis of C-terminal modified peptides by formation of a backbone cyclic urethane moiety

A universal strategy for solid phase synthesis of various C-terminal modified peptides independent of type of resins, unnatural linkers, and handles is developed. Semi-permanent protection at the C-termini of peptides is also afforded by the method described.

Solid Phase Syntheses of Ferulic Acid Derivatives Acetyl Feruloyl Tyrosine and Acetyl Feruloyl Valyl Tyrosine

Ferulic acid was used as a common drug for cardia-cerebrovascular disease and leukopenia, but the application of ferulic acid was inhibited by the poor absorption and stability. The improvement of these defects can be realized by modifying ferulic acid by amino acids, because the amido bond can increase the bioavailability and therapeutic effect of some drugs based on the peptide transporter system of mammalian which can transport the peptidyl drugs. The peptidyl derivatives of ferulic acid, namely acetyl feruloyl tyrosine and acetyl feruloyl valyl tyrosine, were synthesized using Fmoc solid-phase synthesis method. The synthesized ferulic acid amide derivatives were purified by RP-HPLC, and characterized by IR, HNMR and ESI-MS. The results indicated that Fmoc solid phase synthesis was a convenient method for the amide bond modification of ferulic acid and the further property research on ferulic acid derivatives.

Accelerated Fmoc solid-phase synthesis of peptides with aggregation-disrupting backbones

In this work, we describe an accelerated solid-phase synthetic protocol for ordinary or difficult peptides involving air-bath heating and amide protection.