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Conformational studies on beta-amino acid-containing peptides. I
S N Rao1, V N Balaji, K Ramnarayan
1Searle Research and Development, Skokie, IL 60077.
Peptide Research
|November 1, 1992
Summary
Modified amino acids, like beta-amino acids, are key for developing stable peptidomimetics. Our study used computational methods to find low-energy structures, guiding future research in this area.
Area of Science:
- Medicinal Chemistry
- Computational Chemistry
- Biochemistry
Background:
- Modified amino acids, particularly beta-amino acids, are increasingly utilized in drug development.
- These modified amino acids offer advantages in creating orally active and metabolically stable peptidomimetics.
Purpose of the Study:
- To investigate the conformational properties of beta-amino acid-containing compounds.
- To provide insights into the structural characteristics of peptidomimetics incorporating beta-amino acids.
Main Methods:
- Conformational energy calculations were performed using molecular mechanics (MM2) on two model compounds.
- Infrared (IR) spectroscopy data and existing X-ray crystallography data were used for validation.
Main Results:
- Low-energy conformations were identified, characterized by a lack of intramolecular hydrogen bonding.
- Calculated structures were in good agreement with experimental data (IR and X-ray), within 3 kcal/mol of the global minimum.
Conclusions:
- Computational modeling provides valuable insights into the conformational preferences of beta-amino acids in peptidomimetics.
- Preliminary stereochemical guidelines for incorporating beta-amino acid residues were proposed based on the findings.