Carbopeptides: chemoselective ligation of peptide aldehydes to an aminooxy-functionalized D-galactose template.
Multifunctional, topological template molecules such as linear and cyclic peptides have been used for the attachment of peptide strands to form novel protein models of, for example, 4-alpha-helix bundles. The concept of carbohydrates as templates for de novo design of potential protein models has been previously described and these novel chimeric compounds were termed carbopeptides. Here, a second generation strategy in which carbopeptides are synthesized by chemoselective ligation of a peptide aldehyde to an aminooxy-functionalized alpha-D-galactopyranoside is described. This template was prepared by per-O-acylation of methyl alpha-D-galactopyranoside with N,N-Boc2-aminooxyacetic acid to form a tetra-functionalized template, followed by treatment with TFA-CH2Cl2 to release the aminooxy functionality. The peptide aldehydes Fmoc-Ser-Gly-Gly-H and H-Ala-Leu-Ala-Lys-Leu-Gly-Gly-H were synthesized by a BAL strategy. Four identical copies of peptide aldehyde were smoothly attached to the template by chemoselective ligation to form a 2.1 and a 2.9 kDa carbopeptide, respectively.
Brask
J
J
Department of Organic Chemistry, Technical University of Denmark, Lyngby.
Jensen
K J
KJ
D000447:Aldehydes / Q000737:chemistry* / Q000378:metabolism; D002244:Carbon / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D005690:Galactose / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry; D010452:Peptide Biosynthesis; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*
D000447:Aldehydes; D010091:Oximes; D010455:Peptides; D002244:Carbon; D005690:Galactose