Fourth polymorph of [Phe4 Val6] antamanide (pentahydrate)

Area of Science:

• Biochemistry
• Crystallography
• Structural Biology

Background:

• Antamanide is a cyclic decapeptide known for its biological activity.
• Peptide crystallization is influenced by solvent choice, leading to different polymorphic forms.
• Understanding these polymorphs is crucial for drug development and material science.

Purpose of the Study:

• To investigate the crystalline polymorphism of antamanide and its synthetic analog [Phe4 Val6]antamanide.
• To characterize a specific polymorph obtained from acetone/water mixtures.
• To compare the molecular conformation and packing across different crystalline forms.

Main Methods:

• X-ray crystallography was employed to determine the crystal structures.
• Solvent systems including acetone/water, ethanol/water, and DMSO/water were used for crystallization.
• Unit cell parameters and molecular packing were analyzed for different polymorphs.

Main Results:

• A new crystalline polymorph of antamanide analog was obtained from acetone/water, crystallizing in space group P2(1)2(1)2(1).
• This polymorph features specific unit cell dimensions (a = 20.194 Å, b = 21.118 Å, c = 16.132 Å) with four peptide molecules per unit cell.
• Five water molecules were found to be cocrystallized per peptide molecule, with four being intrinsic to the peptide structure.
• Despite different molecular packing in various polymorphs, the conformation of the peptide and its intrinsic water molecules remained highly conserved.

Conclusions:

• Solvent composition significantly influences the crystalline polymorphism of antamanide and its analogs.
• The conserved conformation of the peptide and intrinsic water molecules across different polymorphs suggests a stable structural motif.
• This finding has implications for the rational design and formulation of peptide-based therapeutics.