The synthesis and study of side-chain lactam-bridged peptides.
Side-chain lactam bridges linking amino acid residues that are spaced several residues apart in the linear sequence offer a convenient and flexible method for introducing conformational constraints into a peptide structure. The availability of a variety of selectively cleavable protecting groups for amines and carboxylic acids allows for several approaches to the synthesis of monocyclic, dicyclic, and bicyclic lactam-bridged peptides by solid-phase methods. Multicyclic structures are also accessible, but segment-condensation syntheses with solution-phase cyclizations are most likely to provide the best synthetic approach to these more complex constrained peptides. Lactam bridges linking (i, i + 3)-, (i, i + 4), and (i, i + 7)-spaced residue pairs have all proven useful for stabilization of alpha helices, and (i, i + 3)-linked residues have also been demonstrated to stabilize beta-turns. These structures are finding an increasing number of applications in protein biology, including studies of protein folding, protein aggregation, peptide ligand-receptor recognition, and the development of more potent peptide therapeutics. Defining the functional roles of the amphiphilic alpha-helices in medium-sized peptide hormones, and studying helix propagation from rigid, alpha-helix initiating bicyclic peptides are among the most exciting developments currently underway in this field.
Taylor
John W
JW
Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854, USA. taylor@rutchem.rutgers.edu
D000818:Animals; D006801:Humans; D007769:Lactams / Q000138:chemical synthesis* / Q000378:metabolism; D036361:Peptide Hormones / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis* / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding
D007769:Lactams; D036361:Peptide Hormones; D010455:Peptides