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‐α‐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 α‐D‐galactopyranoside is described. This template was prepared by per‐O‐acylation of methyl α‐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. Copyright © 2000 European Peptide Society and John Wiley & Sons, Ltd.

[1]  W. Haehnel,et al.  Modular synthesis of de novo-designed metalloproteins for light-induced electron transfer. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[2]  F. Albericio,et al.  Backbone Amide Linker (BAL) Strategy for Solid-Phase Synthesis of C-Terminal-Modified and Cyclic Peptides1,2,3 , 1998 .

[3]  W. Haehnel,et al.  Design, Synthesis, and Properties of a Novel Cytochrome b Model , 1998 .

[4]  S. Kent,et al.  EXTENDING THE APPLICABILITY OF NATIVE CHEMICAL LIGATION , 1996 .

[5]  W. DeGrado,et al.  Native-like and structurally characterized designed α-helical bundles , 1995 .

[6]  J. Tam,et al.  Unprotected Peptides as Building Blocks for the Synthesis of Peptide Dendrimers with Oxime, Hydrazone, and Thiazolidine Linkages , 1995 .

[7]  J. Tam,et al.  Chemical Ligation Approach To Form a Peptide Bond between Unprotected Peptide Segments. Concept and Model Study , 1994 .

[8]  Joseph M. Salvino,et al.  De novo design and synthesis of somatostatin non-peptide peptidomimetics utilizing beta-D-glucose as a novel scaffolding , 1993 .

[9]  Stephen F. Betz,et al.  De novo protein design: from molten globules to native-like states , 1993 .

[10]  John T. Groves,et al.  Tetraphilin : a four-helix proton channel built on a tetraphenylporphyrin framework , 1992 .

[11]  Ralph Hirschmann,et al.  Nonpeptidal peptidomimetics with a β-D-glucose scaffolding. A partial somatostatin agonist bearing a close structural relationship to a potent, selective substance P antagonist , 1992 .

[12]  W. DeGrado,et al.  Protein design, a minimalist approach. , 1989, Science.

[13]  M. Mutter,et al.  The Construction of New Proteins. Part III. Artificial folding units by assembly of amphiphilic secondary structures on a template , 1988 .

[14]  K. Jensen,et al.  Carbohydrates as templates for de novo design of proteins , 1995 .

[15]  A. Ferré-D’Amaré,et al.  TOTAL CHEMICAL SYNTHESIS OF A UNIQUE TRANSCRIPTION FACTOR-RELATED PROTEIN : CMYC-MAX , 1995 .

[16]  K. Rose.  Facile synthesis of homogeneous artificial proteins , 1994 .

[17]  U. Ragnarsson,et al.  Preparation and Properties of Nalpha-Di-tert-Butoxycarbonyl Amino Acids. Applicability in the Synthesis of Leu-Enkephalin. , 1990 .

[18]  E. Kaiser,et al.  Helichrome: synthesis and enzymic activity of a designed hemeprotein , 1989 .