Synthesis by Fmoc Chemistry

Synthesis by Fmoc Chemistry

The Fmoc method is a fast and convenient synthesis scheme. Creative Peptides provides services for the entire synthesis process. You can provide us with the PNA sequence you need, and we will design a reasonable synthesis route for customers to help you obtain a satisfactory product.

Chemical Synthesis of PNA Oligomers with Fmoc

Fmoc protected PNA monomer structure.

Fig.1 Fmoc protected PNA monomer structure. (He W.; Ma L.R. 2013)

The first synthesis of PNA was done by solid-phase synthesis using classical Boc chemistry, which has many advantages, including better synthetic quality, but involves the use of some hazardous chemicals. The Fmoc solution can provide high-quality synthetic products, and can avoid the use of strong corrosive chemicals in Boc technology, so Fmoc SPPS has become a commercially popular synthetic technology. The Fmoc group has obvious selectivity for the protection of the aliphatic primary ammonia of the PNA monomer, Bhoc has the protection of the exocyclic amino group of the nucleobases A, C and G. At present, the Fmoc/Bhoc PNA monomer can be directly available on the market.

Our Service Process

The Fmoc-based PNA synthesis route consists of repeated cycles of deprotection, activation, coupling and capping, as shown in Figure 2. The direction of synthesis is from the C terminal (carboxyl terminal) to the N terminal (amino terminal). In order to prevent side reactions, the synthetic column and the side chains of the added amino acid are maintained in advance. Only the carboxyl terminal is free, and It is necessary to activate it with chemical reagents before the reaction. In addition, solid-phase synthesis also greatly reduces the difficulty of commercial purification.

PNA synthesis cycle

Fig.2 PNA synthesis cycle (He W.; Ma L.R. 2013)

  • Deprotection. Depending on the residues contained in the peptide chain, it is eluted from the column with a different resin-removing solvent, and its maintenance group is eluted and de-maintained by a de-maintaining agent (TFA).
  • Coupling.The carboxyl group of the next amino acid is activated and dissolved by an activator, and the activated monomer and free amino group are cross-linked under the action of the cross-linking agent to form a peptide bond.
  • Capping. Use an alkaline solvent (piperidine) to remove the maintenance group of amino group of the Fmoc-protected column and the monomer.
  • Cycle:The above reaction repeats the cycle until the synthesis of the entire peptide nucleic acid chain is completed.


  • Quick and easy synthesis of small-scale PNA oligomers, which can be performed on common DNA synthesis platforms.
  • Using alkali-removable Fmoc as the protective group of α-amino group, TFA-removable tert-butoxy group to protect the side chain, 90% TFA-removable p-alkoxybenzyl alcohol resin. The final deprotection avoids strong acid treatment.
  • It is easy to prepare a wide range of PNA with fluorescent labels and other sensitive reporter groups.

Creative Peptides scientists are committed to meeting our customers' needs for PNA synthesis. If you need more detailed information, please feel free to contact us to see how we can help you achieve the desired PNA oligomer synthesis.


  • He W.; Ma L.R. Peptide nucleic acid. Chemical Industry Press.2003.

Notice: Products and services are used only for scientific research.