Carbopeptides: chemoselective ligation of peptide aldehydes to an aminooxy-functionalized D-galactose template

Brask, Jesper; Jensen, Knud J.

doi:10.1002/1099-1387(200006)6:6<290::aid-psc257>3.0.co;2-l

Cited by 48 publications

(45 citation statements)

References 26 publications

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“…This allowed reliable preparation of 10-20 mg of purified carboprotein on Galp, Glcp, and Altp templates ( Figure 15). 98,99 Biophysical studies with CD and H-D exchange NMR spectroscopy clearly indicated formation of the desired 4--helix bundle. Surprisingly, a carboprotein assembled on an Altp template showed a higher content of -helix compared to similar carboproteins prepared on Galp and Glcp.…”

Section: Carboproteins: Protein Models On Carbohydrate Templatesmentioning

confidence: 96%

Carbohydrates in peptide and protein design

Jensen¹,

Brask²

2005

Biopolymers

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Monosaccharides and amino acids are fundamental building blocks in the assembly of nature's polymers. They have different structural aspects and, to a significant extent, different functional groups. Oligomerization gives rise to oligosaccharides and peptides, respectively. While carbohydrates and peptides can be found conjoined in nature, e.g., in glycopeptides, the aim of this review is the radical redesign of peptide structures using carbohydrates, particularly monosaccharides and cyclic oligosaccharides, to produce novel peptides, peptidomimetics, and abiotic proteins. These hybrid molecules, chimeras, have properties arising largely from the combination of structural characteristics of carbohydrates with the functional group diversity of peptides. This field includes de novo designed synthetic glycopeptides, sugar (carbohydrate) amino acids, carbohydrate scaffolds for nonpeptidal peptidomimetics of cyclic peptides, cyclodextrin functionalized peptides, and carboproteins, i.e., carbohydrate-based proteinmimetics. These successful applications demonstrate the general utility of carbohydrates in peptide and protein architecture. #

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Section: Carboproteins: Protein Models On Carbohydrate Templatesmentioning

confidence: 96%

Carbohydrates in peptide and protein design

Jensen¹,

Brask²

2005

Biopolymers

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“…The carbopeptide concept was extended in a second-generation approach with the goal to prepare protein-sized structures, starting with the relatively well-understood 4-a-helix bundles [56,57]. Inspired by the progress in chemoselective ligation chemistry, a convergent modular synthesis strategy was adopted to increase the freedom of the design.…”

Section: The Second Generationmentioning

confidence: 99%

“…Boc groups are advantageous, as normally no purification step is required after deprotection and precedents existed for N,N-di-Boc protection of amino acids [61]. Accordingly, Boc 2 -Aoa-OH was synthesized in high yield from BocAoa-OH in three facile steps with transient protection of the carboxylic acid as the benzyl ester and incorporation of the second Boc group in the presence of DMAP [56]. With Boc 2 -Aoa-OH in hand, the protected template was readily prepared in good yield by DIPCDI/DMAP-mediated coupling in pyridine-CH 2 Cl 2 (1:1); gratifyingly, final removal of all eight Boc groups with TFA-CH 2 Cl 2 (1:1) proved to be fast and quantitative to provide the desired compound, methyl 2,3,4,6-tetra-O-Aoa-a-D-Galp (6) ( fig.…”

Section: The Second Generationmentioning

confidence: 99%

“…With Boc 2 -Aoa-OH in hand, the protected template was readily prepared in good yield by DIPCDI/DMAP-mediated coupling in pyridine-CH 2 Cl 2 (1:1); gratifyingly, final removal of all eight Boc groups with TFA-CH 2 Cl 2 (1:1) proved to be fast and quantitative to provide the desired compound, methyl 2,3,4,6-tetra-O-Aoa-a-D-Galp (6) ( fig. 4) [56]. This tetra-functionalized template should This is a simplified illustration, as the peptide stands are aligned in parallel (i. e., no interhelical crossover) and locked in a-helical conformation, with only the template structure being energy minimized (Tripos force field).…”

Section: The Second Generationmentioning

confidence: 99%

“…A number of C-terminal peptide aldehydes have been synthesized for second-generation carboproteins, starting with the shorter sequences Fmoc-Ser-Gly-Gly-H (8) and HAla-Leu-Ala-Lys-Leu-Gly-Gly-H (9) [56], and later extended to the dodeca-and hexadecapeptide aldehydes AcLys-Ala-Leu-Lys-Glu-Ala-Leu-Ala-Lys-Leu-Gly-Gly-H (10) and Ac-Glu-Ala-Leu-Glu-Lys-Ala-Leu-Lys-Glu-AlaLeu-Ala-Lys-Leu-Gly-Gly-H (11) [57]. Briefly, the syntheses followed a standard BAL strategy [58,59,62], commencing with coupling of a PALdehyde handle to aminofunctionalized resin, followed by anchoring of the glycinal terminal by reductive amination with aminoacetaldehyde dimethyl acetal.…”

Section: The Second Generationmentioning

confidence: 99%

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Carbohydrates as templates for control of distance-geometry in de novo-designed proteins

Jensen¹,

Brask

2002

CMLS, Cell. Mol. Life Sci.

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An understanding of very complex natural systems can often only be achieved through detailed studies of systems with a reduced complexity. Thus, de novo design of proteins allows the study of fundamental forces determining protein folding and stability, as well as protein-protein interactions, by analyses of protein models of structural motifs. In addition, de novo design may lead to new biomimetic molecules with novel properties. In a synthetic approach to achieve structural economy, rigid templates, sometimes called topological scaffolds, have been used to connect secondary-structure elements, most notably alpha-helices. By positioning the helices on the template, the unfavorable entropy of protein folding is reduced. In a novel class of chimeric molecules called carboproteins, carbohydrates are used as templates for de novo design of protein models. Recently, a strategy relying on chemoselective ligation of C-terminal peptide aldehydes to tetra-aminooxy functionalized monosaccharides has provided 7-kDa 4-alpha-helix bundle carboproteins.

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Carbohydrates in Peptide and Protein Design

Jensen

Brask

2009

Peptide and Protein Design for Biopharmaceutical Applications

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Carbopeptides: chemoselective ligation of peptide aldehydes to an aminooxy-functionalized D-galactose template

Cited by 48 publications

References 26 publications

Carbohydrates in peptide and protein design

Carbohydrates in peptide and protein design

Carbohydrates as templates for control of distance-geometry in de novo-designed proteins

Carbohydrates in Peptide and Protein Design

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