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Updated: Jun 22, 2025
07:11
Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
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Structural insights into somatostatin receptor 5 bound with cyclic peptides
Ying-Ge Li1, Xian-Yu Meng1, Xiru Yang1
1The First Affiliated Hospital of USTC, School of Life Sciences, Division of Life Sciences and Medicine, Joint Center for Biological Analytical Chemistry, Anhui Engineering Laboratory of Peptide Drug, Anhui Laboratory of Advanced Photonic Science and Technology, University of Science and Technology of China, Hefei, 230026, China.
Acta Pharmacologica Sinica
|June 26, 2024
Summary
Structural insights reveal how pasireotide and octreotide bind to somatostatin receptor 5 (SSTR5). Understanding these mechanisms is key for developing selective drugs targeting SSTR5 for Cushing's disease treatment.
Area of Science:
- Biochemistry
- Structural Biology
- Pharmacology
Background:
- Somatostatin receptor 5 (SSTR5) is a key target for Cushing's disease treatment.
- Current drugs like pasireotide and octreotide lack SSTR5 selectivity, causing side effects.
- Understanding ligand-receptor interactions is crucial for developing selective drugs.
Purpose of the Study:
- To elucidate the molecular mechanisms of pasireotide and octreotide binding to SSTR5.
- To provide structural basis for the development of selective SSTR5-targeting drugs.
Main Methods:
- Cryo-electron microscopy (cryo-EM) to determine SSTR5-Gi complex structures.
- Structural analysis and functional experiments to understand ligand recognition and receptor activation.
Main Results:
- Two cryo-EM structures of SSTR5-Gi complexes with pasireotide and octreotide were determined.
- Pasireotide shows preferential binding to SSTR5 via specific interactions.
- Specific residues and regions in SSTR2 are critical for octreotide's biased binding.
Conclusions:
- The study reveals the molecular basis of pasireotide and octreotide interactions with SSTR5.
- Findings offer structural insights for designing subtype-selective somatostatin analog drugs.
- This research paves the way for improved therapeutics for SSTR5-related conditions like Cushing's disease.
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