A new hydrazone resin enables a convenient way to synthesize peptide hydrazides for Hydrazone Ligation Technique and Native Chemical Ligation (NCL).

Technology for the Synthesis of Peptide Thioesters

Peptide hydrazides can be easily synthesized using a new hydrazone resin. It was shown that the hydrazone linker is completely stable in the course of standard Fmoc SPPS. Moreover, it can tolerate a treatment with 5% TFA/DCM thus permitting selective removal of Mtt or related acid-labile protecting groups. Subsequent application of cleavage cocktails containing net TFA permits to obtain the desired peptides in excellent yields and purity.

Synthesized peptide hydrazides can be applied as building blocks for the conjugation with different carrier molecules using hydrazone ligation technique:

Hydrazides can be converted into peptide azides as precursors for the formation of appropriate peptide thio esters used in native chemical ligation (NCL):

In order to prove the practical utility of this resin, a set of model compounds have been synthesized (Fmoc/But strategy; cleaved with TFA/H2O/TIS (95:2.5:2.5 v/v/v)) including the nuclear localization signal (NLS) of large T-antigen of SV-40 virus, tuftsin, so-called Szeto-Schiller peptide, and two precursors for the synthesis of self-assembling peptides containing RADA repeats. All selected compounds contain Arg residues, complicating direct preparation of hydrazides by means of hydrazinolysis. The results demonstrate a very convenient approach to prepare peptide hydrazides useful for different ligation techniques.

The properties of Hydrazone Resins:

• Compatible with standard Fmoc SPPS;
• Permitting selective removal of Mtt for side chain modifications;
• High yield of peptide-hydrazides even of peptides with several Arginines.
• Convenient way to synthesize peptide hydrazides for Hydrazone Ligation and Native Chemical Ligation (NCL).

➔ Find all available hydrazone base resin and preloaded resins here.

• Convenient method of peptide hydrazide synthesis using a new hydrazone resin; Pavel S. Chelushkin, Ksenia V. Polyanichko, Maria V. Leko, Marina Yu. Dorosh, Thomas Bruckdorfer, Sergey V. Burov; Tetrahedron Letters 2015; 56: 619–622. http://dx.doi.org/10.1016/j.tetlet.2014.12.056