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Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
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Development of cyclic NGR peptides with thioether linkage: structure and dynamics determining deamidation and
Kata Nóra Enyedi1, András Czajlik, Krisztina Knapp
1MTA-ELTE Research Group of Peptide Chemistry, Hungarian Academy of Sciences,▽MTA-ELTE Protein Modelling Research Group, Hungarian Academy of Sciences, ∥Laboratory for Chiroptical Structure Analysis, Institute of Chemistry, and ⊥Laboratory of Structural Chemistry and Biology, Institute of Chemistry, Eötvös Loránd University , Pázmány P. sétány 1/A, 1117 Budapest, Hungary.
Journal of Medicinal Chemistry
|February 4, 2015
Summary
Novel cyclic NGR peptides targeting tumor neovasculature show improved stability. Their structure, particularly Asn side-chain orientation, dictates resistance to decomposition and influences cell adhesion properties.
Area of Science:
- Biochemistry
- Medicinal Chemistry
- Oncology
Background:
- NGR peptides targeting CD13 receptors in tumor neovasculature are promising for drug delivery.
- Understanding peptide stability is crucial for effective therapeutic applications.
Purpose of the Study:
- To synthesize and analyze novel thioether bond-linked cyclic NGR peptides.
- To investigate the factors influencing their chemical stability and biological activity.
Main Methods:
- Synthesis of novel cyclic NGR peptides.
- Structural analysis using spectroscopic and crystallographic methods.
- Assessment of chemostability under various conditions.
- Evaluation of cell adhesion effects on A2058 melanoma cell lines.
Main Results:
- Chemostability strongly depends on sample handling and structural properties, notably the Asn side-chain orientation.
- Increased chemostability correlates with specific structural measures like NH(Gly)-CO(Asn-sc) distances.
- Structure-stabilizing factors, such as hydrogen bonds, enhance resistance to decomposition.
- Some cyclic NGR peptides increased melanoma cell adhesion, suggesting time-dependent formation of integrin-binding isoAsp derivatives.
Conclusions:
- Thioether bond-linked cyclic NGR peptides can be engineered for enhanced stability.
- Peptide structure, particularly Asn side-chain orientation, is a critical determinant of chemostability.
- The observed cell adhesion effects highlight the potential for NGR peptides in modulating tumor cell interactions.
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