β-Cyclodextrin derivatives bind aromatic side chains of the cyclic peptide lanreotide

Area of Science:

• Pharmaceutical Sciences
• Supramolecular Chemistry
• Drug Delivery Systems

Background:

• Cyclodextrins (CDs) are widely used to improve drug solubility and stability.
• Peptide drugs, like lanreotide acetate, can form inclusion complexes with CDs, modulating their physicochemical properties.
• Understanding CD-peptide interactions is crucial for developing effective peptide-based therapeutics.

Purpose of the Study:

• To investigate the inclusion complexation of lanreotide acetate with Sulfobutyl ether β-CD (SBEβ-CD) and hydroxypropyl β-CD (HPβ-CD).
• To elucidate the binding interactions between lanreotide acetate and these cyclodextrin derivatives at a molecular level.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy was employed to study the interactions.
• Diffusion ordered spectroscopy (DOSY) NMR was used to determine changes in diffusion coefficients and hydrodynamic radii.
• Alanine substitution studies and molecular docking simulations were performed to analyze binding affinities and complex conformations.

Main Results:

• NMR confirmed that hydrophobic aromatic residues of lanreotide acetate fit into the cavities of both SBEβ-CD and HPβ-CD.
• Complexation led to decreased diffusion coefficients and increased hydrodynamic radii, indicating successful binding.
• SBEβ-CD demonstrated stronger binding affinity to lanreotide acetate compared to HPβ-CD.
• Docking studies favored 1:1 inclusion complexes and showed stable conformations for aromatic side chains within both CDs.

Conclusions:

• Both SBEβ-CD and HPβ-CD can form inclusion complexes with lanreotide acetate, with SBEβ-CD exhibiting superior binding.
• The hydrophobic interactions of aromatic residues play a key role in the complexation process.
• These findings provide valuable insights for the formulation and development of lanreotide acetate using cyclodextrin-based drug delivery systems.