Synthesis and application of β-amino γ-lactams in the study of interleukin-1 and cluster of differentiation-36 receptors modulating peptides

In the study of peptide structure-activity relationships, the α-amino γ-lactam (Agl), so-called Freidinger-Veber lactam residues are important tools due in part to ability to favour β-turn conformers (Figure) [1]. In examinations of peptide molecular recognition, the β-amino γ-lactam (Bgl) residue has been less commonly used as the Agl counterpart but offers similar potential to stabilize turn conformers [2]. For example, notable activity has been exhibited by Bgl analogs of allosteric modulators of the interleukin-1 and the cluster of differentiation-36 receptors (IL-1R and CD-36) [2, 3]. Our presentation will describe advances in the synthesis and application of Bgl residues for studying peptide conformation and activity.

References

1. Freidinger, R. M.; Veber, D. F.; Perlow, D. S.; Brooks, J. R., Bioactive conformation of luteinizing hormone-releasing hormone: evidence from a conformationally constrained analog. Science 1980, 210 (4470), 656-658.
2. Boutard, N.; Turcotte, S.; Beauregard, K.; Quiniou, C.; Chemtob, S.; Lubell, W. D., Examination of the active secondary structure of the peptide 101.10, an allosteric modulator of the interleukin‐1 receptor, by positional scanning using β‐amino γ‐lactams. Pept. Sci. 2011, 17 (4), 288-296.
3. Boutard, N.; Jamieson, A. G.; Ong, H.; Lubell, W. D., Structure–Activity Analysis of the Growth Hormone Secretagogue GHRP-6 by α- and β-Amino γ-Lactam Positional Scanning. Biol. Drug Des. 2010, 75 (1), 40-50.