Modification with Cyclic Structure
Introducing the cyclic structure into PNA is one of the important methods to obtain skeleton-modified PNA, mainly choosing the more stable five-membered ring and six-membered ring. Among them, the PNA with a five-membered ring has attracted people's attention because its structure better mimics the pentose ring in DNA.
Introduce Five-membered Ring Structure
|N-(2-Boc Aminoethyl) Alanine
1. Using natural trans-4-hydroxy-L-proline as raw material, firstly protect the 2-position secondary amino group on the ring, convert the 1-position carboxyl group into methylamine and protect this amino group with Boc.
|In the synthesis, 4-hydroxy-L-proline or tetrahydropyrrole derivatives are used as raw materials, and 4-hydroxy-L-proline functional groups (1-position carboxyl group, 2-position secondary amino group, 4-position hydroxyl group) are used as raw materials active groups participate in the reaction.
Introduce Six-membered Ring Structure
|Six-membered piperidinane ring structure
|1. Cis-5S-hydroxy-2-2s-N-1-benzyloxycarbonyl pipecolic acid methyl ester as raw material, first remove the N-1 protective group.
2. Then with the N-Boc aminoethyl acylated with methanesulfonic acid to carry out the alkylation reaction of the nitrogen atom on the piperidine ring to obtain the derivative of (N-Boc aminoethyl) pipecolic acid methyl ester.
3. Using Mitsunobu reaction to replace the C-5 (S) hydroxyl functional group with N-3 benzyloxythymidine to obtain (2S,5R)-5-(N-3-benzyloxythymidine) pipecolic acid methyl ester derivative.
4. Finally, the target monomer (2S, 5R)-1-N-aminoethyl-5-thymine pipecolic acid is obtained by saponification with sodium hydroxide.
|Six-membered aromatic ring
|1. Using 2-aminomethylaniline as the raw material, first use Boc to selectively protect the amino group attached to the methyl group, and then use the allyl group to protect the 1-amino group.
2. The Boc is then removed, the amino group attached to the methyl group is exposed, the skeleton is formed by the alkylation reaction with tert-butyl bromoacetate, and then it is condensed with basic acetic acid to obtain a monomer with protected amino and carboxyl groups.
3. Finally, the amino protecting group is converted to Fmoc protection, and then the carboxyl group is deprotected to obtain the target monomer.
- The modified skeleton structure can be protonated, which is conducive to the cell transport of PNA, and also has good water solubility.
- For PNA monomers with a cyclic structure in the backbone, the three-dimensional configuration has a greater impact on the Tm value, and some new structures can control the stability of the hybridization process.
- Other advantages include increased cell membrane permeability and improved binding affinity.
Creative Peptides can provide PNA modification services, including the modification of the skeleton structure. According to your needs, we can design and give you a reasonable modification plan in order to achieve the functions you need. We are committed to providing you with timely, high-quality deliverables. At the same time, we guarantee cost-effective, complete and concise reports. If you have any need for PNA synthesis and modification, please feel free to contact us.
- He Y.X. et al.Research progress of monomer skeleton modification of peptide nucleic acids. Chinese journal of medicinal chemistry. 2006, 16(4):253-258.
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