info@cytosynthesis.com
search

Fmoc-NHN=Pyv Resin

Chemical name:
Fmoc-hydrazono-pyruvyl-aminomethylpolystyrene resin
Particle size:
100-200 mesh
DVB crosslinking:
1% DVB
Loading:
> 0.3 mmol/g
Quantity:
Price:
on request
 

Application

This new hydrazone resin provides a new and convenient method for the synthesis of peptide hydrazides, which can be applied in ligation or fragment condensation technique. It was shown that the hydrazone linker is completely stable in the course of standard Fmoc SPPS. Moreover, it can tolerate 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 reasonable yields and purity.

References

  1. Convenient method of peptide hydrazide synthesis using a new hydrazone resin; P.S. Chelushkin, K.V. Polyanichko, M.V. Leko, M.Yu. Dorosh, Thomas Bruckdorfer, S.V. Burov; Tet. Lett. 2015; 56: 619-622. DOI: 10.1016/j.tetlet.2014.12.056.
  2. Synthesis of dendronized polymeric chelating agents using hydrazone ligation strategy; K.V. Polyanichko, P.S. Chelushkin, M.Yu. Dorosh, I.I. Gavrilova, Evgeny Panarin, A.V. Dobrodumov, S.V. Burov; European Polymer Journal 2017; 92: 117–125. DOI: 10.1016/j.eurpolymj.2017.04.040.

Attachment of the First Amino Acid on Hydrazone Resin

Method 1

  1. Place Fmoc-NHN=Pyv resin in a clean dry reaction vessel, add sufficient DMF and allow to swell for 1 h.
  2. Wash the resin with DMF and treat with 20% piperidine in DMF (1×2 min; 1×8 min) to remove Fmoc group. Wash with DMF (2×1 min); i-PrOH (2×1 min) and DMF (3×1 min).
  3. Dissolve Fmoc amino acid (4 eq.) and Oxyma Pure (4 eq.) in DMF with stirring at room temperature and cool to 0 °C in an ice bath. Add DIC (4 eq.) and stir the reaction mixture for 10 min.
  4. Transfer the solution of activated Fmoc amino acid to the reaction vessel containing the resin. Stir for 60 min and leave overnight. Wash the resin with DMF (3×1 min).
  5. Perform the Fmoc loading test. If necessary, repeat the points 3 and 4.

Method 2*

  1. Place Fmoc-NHN=Pyv resin in a clean dry reaction vessel, add sufficient DMF and allow to swell for 1 h.
  2. Wash the resin with DMF and treat with 20% piperidine in DMF (1×2 min; 1×8 min) to remove Fmoc group. Wash with DMF (2×1 min); i-PrOH (2×1 min) and DMF (3×1 min).
  3. Dissolve Fmoc amino acid (4 eq.) and PyAOP (4 eq.) in DMF with stirring at room temperature, add DIEA (8 eq.) and stir the reaction mixture for 8 min.
  4. Transfer the solution of activated Fmoc amino acid to the reaction vessel containing the resin. Stir for 60 min and leave overnight. Wash the resin with DMF (3×1 min).
  5. Perform the Fmoc loading test. If necessary, repeat the points 3 and 4.
* The method is not suitable in the case of Ser and Cys due to the partial racemization.

Notes

The formation of truncated peptide sequences was not observed so far, however the residual hydrazone groups can be capped using Ac2O/DIEA/DCM mixture.
Close