Facile access to modified and functionalized PNAs through Ugi-based solid phase oligomerization.

Area of Science:

• Biochemistry
• Organic Chemistry
• Materials Science

Background:

• Peptide nucleic acids (PNAs) are versatile molecules with increasing use in supramolecular chemistry.
• PNAs exhibit high tolerance to chemical modifications, enhancing their applicability.
• Modifications, especially at the gamma position, are crucial for PNA functionality.

Purpose of the Study:

• To develop simple protocols for synthesizing modified PNAs.
• To enable modular modifications at the alpha, beta, or gamma positions of the PNA backbone.
• To demonstrate the utility of the developed method through the synthesis of PNA conjugates.

Main Methods:

• Iterative Ugi couplings were employed for PNA synthesis.
• Simple starting materials were utilized for PNA backbone modification.
• The method allowed for modular incorporation of functional groups at specific PNA positions.

Main Results:

• Protocols for accessing modified PNAs were successfully established.
• Modular modifications at alpha, beta, and gamma positions were achieved.
• Several bioactive small molecule-PNA conjugates, including a peptide ligand, kinase inhibitor, and glycan, were synthesized.

Conclusions:

• The developed Ugi coupling-based method provides a straightforward route to diverse modified PNAs.
• This approach facilitates the modular synthesis of functionalized PNAs for various applications.
• The synthesis of bioactive small molecule-PNA conjugates highlights the method's practical utility.