Folding and function in α/β-peptides: targets and therapeutic applications

Area of Science:

• Biochemistry
• Medicinal Chemistry
• Molecular Biology

Background:

• Natural peptides and proteins are crucial biological molecules but are often susceptible to enzymatic degradation.
• Heterogeneous-backbone oligomers, termed alpha/beta-peptides, integrate natural alpha-amino acids and unnatural beta-amino acids.
• These alpha/beta-peptides can adopt diverse folding patterns and biological functions similar to natural peptides.

Purpose of the Study:

• To explore the potential of alpha/beta-peptides as stable and functional biomolecules.
• To investigate the therapeutic applications of alpha/beta-peptides in various biological systems.
• To highlight the advantages of incorporating beta-amino acids for enhanced peptide stability.

Main Methods:

• Synthesis of alpha/beta-peptide chains incorporating both alpha- and beta-amino acid residues.
• Characterization of the folding patterns and conformational properties of alpha/beta-peptides.
• Evaluation of biological activity and stability against protease degradation in vitro and in vivo.

Main Results:

• Alpha/beta-peptides demonstrate diverse folding capabilities, mimicking natural peptide structures.
• Incorporation of beta-residues significantly enhances stability against protease degradation.
• Developed alpha/beta-peptides show efficacy against targets in apoptotic signalling, HIV-cell fusion, hormone signalling, and angiogenesis.
• In vivo studies confirm potent and prolonged activity of alpha/beta-peptides compared to alpha-peptide counterparts.

Conclusions:

• Alpha/beta-peptides represent a promising class of molecules with inherent stability and versatile biological functions.
• Their ability to engage diverse therapeutic targets and exhibit enhanced in vivo performance makes them attractive drug candidates.
• Further development of alpha/beta-peptides holds significant potential for advancing therapeutic strategies.