Synthesis and helical structure of lactam bridged BH3 peptides derived from pro-apoptotic Bcl-2 family proteins.
Protein-protein interactions within the Bcl-2 family are mediated by the helical BH3 domains of pro-apoptotic family members. To study the mechanism of this BH3 domain-protein interaction, a series of cyclic lactam bridged BH3 peptide analogues were synthesized by a novel combined Fmoc/tBu/Bzl protections strategy. These peptide analogues were studied by circular dichroism spectroscopy and found to adopt highly helical structure. These helical peptides stabilized by a lactam bridge serve as useful models to analyze the structure-function relationship of the pro-apoptotic BH3 domains. Furthermore, the synthetic method for lactam bridge incorporation reported here may find application in studies of other helical structures and development of helix mimics.
Yang
Bin
B
Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Liu
Dongxiang
D
Huang
Ziwei
Z
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D007769:Lactams / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry* / Q000235:genetics
C474007:Bax protein (53-86); D007769:Lactams; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2