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Facile Protocol for the Synthesis of Self-assembling Polyamine-based Peptide Amphiphiles PPAs and Related Biomaterials
Published on: June 25, 2018
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Exploring Secondary Amine Carnosine Derivatives: Design, Synthesis, and Properties.
Angelica Artasensi1, Sarah Mazzotta1,2, Ines Sanz1
1Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via L. Mangiagalli 25, 20133 Milan, Italy.
Molecules (Basel, Switzerland)
|November 9, 2024
Summary
Researchers explored modifying carnosine to enhance its bioavailability in humans. Targeting the amino group, they aimed to create carnosine derivatives resistant to human serum carnosinase while retaining therapeutic activity against toxic electrophiles.
Area of Science:
- Biochemistry
- Pharmacology
- Medicinal Chemistry
Background:
- Carnosine, a natural dipeptide, shows therapeutic potential in animal models by neutralizing toxic electrophiles like 4-hydroxynonenal (HNE).
- Human bioavailability of carnosine is limited due to rapid hydrolysis by the enzyme human serum carnosinase (HSC).
- Existing strategies focus on carnosinase-resistant carnosine derivatives, but modification of the N-terminus amino group, crucial for activity, is underexplored.
Purpose of the Study:
- To investigate the modification of carnosine's N-terminus amino group.
- To develop carnosinase-resistant carnosine derivatives.
- To assess if these derivatives retain electrophile-scavenging activity.
Main Methods:
- Chemical synthesis of carnosine derivatives with modified N-terminus.
- Assessment of resistance to human serum carnosinase hydrolysis.
- Evaluation of the binding activity toward toxic electrophiles, such as HNE.
Main Results:
- Some N-terminus modifications resulted in inactive compounds, confirming the group's importance for scavenging.
- Certain derivatives demonstrated resistance to carnosinase hydrolysis.
- The study explored the feasibility of modifying the N-terminus while preserving therapeutic efficacy.
Conclusions:
- Modifying carnosine's N-terminus amino group presents challenges for retaining electrophile-scavenging activity.
- Developing carnosinase-resistant carnosine derivatives requires careful consideration of the N-terminus role.
- Further research is needed to balance bioavailability enhancement with preserved therapeutic function.
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