Conformational studies and stereochemical assignment of a bicyclic lactam-containing peptide fragment by two-dimensional NMR spectroscopy

The stereochemistry and conformation of a key bicyclic lactam-based Leu-Pro building block and the conformation of the surrounding peptide fragment were assigned using a combination of 2D-NOE data and coupling constants from an NMR simulation. The work confirmed that the initial stereochemistry of the building block had not been lost during its incorporation into the peptide. The proline portion of the building block was found to be in a predominantly endo conformation. The six-membered ring lactam that was used to constrain the leucine portion of the building block was found to be in a half-chair conformation. The peptide fragment on both sides of the building block was found to be in an extended conformation.