Synthesis of Glycopeptides and Lipopeptides by Chemoselective Ligation

Cervigni, Stefano E.; Dumy, Pascal; Mutter, Manfred

doi:10.1002/anie.199612301

Cited by 125 publications

(70 citation statements)

References 21 publications

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“…As a second illustrative example for the use of HCan building blocks in chemoselective ligation chemistry, a glycopeptide as a prototype for chimeric molecules [19] was prepared (Scheme 3. In analogy to the linear decapeptide above, the tetrapeptide HScheme 2 Synthesis of the cyclic decapeptide containing two Aloc-protected HCan residues showing the orthogonally addressable side chains.…”

Section: Hcan In Peptide Synthesismentioning

confidence: 99%

Chemoselectively addressable HCan building blocks in peptide synthesis:L-homocanaline derivatives

et al. 1998

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(S-2-amino-5-(aminooxy)pentanoic acid (L-homocanaline, HCan), a structural analogue of lysine, contains a reactive alkyloxyamine side chain and is therefore considered to react chemoselectively with carbonyl compounds by forming a kinetically stable oxime bond. The chemical synthesis of L-homocanaline starting from protected glutamic acid derivatives is described. Two orthogonally protected homocanaline derivatives were synthesized and their use in standard SPPS procedures was exemplified for the synthesis of a chemoselectively addressable cyclic peptide for use in TASP design. Moreover, the wide range of applications of this unique building block was demonstrated for the chemoselective ligation of an unprotected disaccharide to a HCan containing model peptide resulting in a chimeric glycopeptide structure.

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Section: Hcan In Peptide Synthesismentioning

confidence: 99%

Chemoselectively addressable HCan building blocks in peptide synthesis:L-homocanaline derivatives

et al. 1998

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“…[15] It is also possible to link a peptide bearing an aminooxy function to the anomeric center of a free aldose in a chemoselective way, that is, without use of protecting groups. [16] It is well known that when using a reacting unit bearing a ™primary∫ À O À NH 2 group, an open-chain sugar oxime is obtained, [17] but it has also been observed that the cyclic form of the sugar is restored when a peptide with a ™secondary∫ hydroxylamino group (RÀOÀNHÀR') is used. [18] By following this last approach, if R and R' were sugar units, it would be possible in principle to obtain disaccharides and, more generally, oligosaccharide mimics by working in water and avoiding the use of any activation and protection strategy.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Conformational Analysis of Novel N(OCH₃)‐linked Disaccharide Analogues

Peri

Jiménez‐Barbero

Garcı́a-Aparicio

et al. 2004

Chemistry A European J

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N(OMe)-linked disaccharide analogues, isosteric to the corresponding natural disaccharides, have been synthesized by chemoselective assembly of unprotected natural monosaccharides with methyl 6-deoxy-6-methoxyamino-alpha-D-glucopyranoside in an aqueous environment. The coupling reactions were found to be chemo- and stereoselective affording beta-(1-->6) disaccharide mimics when using Glc and GlcNAc; in the case of Gal, the beta-anomer was prevalent (beta:alpha=7:1). An iterative method for the synthesis of linear N(OMe) oligosaccharide analogues was demonstrated, based on the use of an unprotected monosaccharide building block in which an oxime functionality at C-6 is converted during the synthesis into the corresponding methoxyamino group. The conformational analysis of these compounds was carried out by using NMR spectroscopy, ab initio, molecular mechanics, and molecular dynamics methods. Optimized geometries and energies of fourteen conformers for each compound have been calculated at the B3LYP/6-31G* level. Predicted conformational equilibria were compared with the results based on NMR experiments and good agreement was found. It appears that N(OMe)-linked disaccharide analogues exhibit a slightly different conformational behavior to their parent natural disaccharides.

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“…In early examples of this chemoselective reaction, sugars and peptides that contain secondary alkoxylamines were reacted with Dglucose, D-mannose, D-galactose, lactose, and N-acetyl-Dglucosamine to generate oligosaccharide and glycopeptide mimics, respectively (12,13). These pioneering studies revealed that, unlike primary alkoxylamines, which provide open-chain oxime isomers (14), secondary alkoxylamines react to form closed-ring neoglycosides (Fig. 1B).…”

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Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization

Langenhan¹,

Peters²,

Guzei³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

218

174

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Glycosylated natural products are reliable platforms for the development of many front-line drugs, yet our understanding of the relationship between attached sugars and biological activity is limited by the availability of convenient glycosylation methods. When a universal chemical glycosylation method that employs reducing sugars and requires no protection or activation is used, the glycorandomization of digitoxin leads to analogs that display significantly enhanced potency and tumor specificity and suggests a divergent mechanistic relationship between cardiac glycosideinduced cytotoxicity and Na ؉ ͞K ؉ -ATPase inhibition. This report highlights the remarkable advantages of glycorandomization as a powerful tool in glycobiology and drug discovery.carbohydrate ͉ natural product ͉ sugar

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Synthesis of Glycopeptides and Lipopeptides by Chemoselective Ligation

Abstract: Completely unprotected peptides carrying chemoselectively addressable groups react under very mild conditions with free reducing sugars or lipidic aldehydes to form glycopeptides or lipopeptides (for example the somatostatin analogue 1) of any desired structural complexity.

Cited by 125 publications

References 21 publications

Chemoselectively addressable HCan building blocks in peptide synthesis:L-homocanaline derivatives

Chemoselectively addressable HCan building blocks in peptide synthesis:L-homocanaline derivatives

Synthesis and Conformational Analysis of Novel N(OCH₃)‐linked Disaccharide Analogues

Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization

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Synthesis of Glycopeptides and Lipopeptides by Chemoselective Ligation

Abstract: Completely unprotected peptides carrying chemoselectively addressable groups react under very mild conditions with free reducing sugars or lipidic aldehydes to form glycopeptides or lipopeptides (for example the somatostatin analogue 1) of any desired structural complexity.

Cited by 125 publications

References 21 publications

Chemoselectively addressable HCan building blocks in peptide synthesis:L-homocanaline derivatives

Chemoselectively addressable HCan building blocks in peptide synthesis:L-homocanaline derivatives

Synthesis and Conformational Analysis of Novel N(OCH3)‐linked Disaccharide Analogues

Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization

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Synthesis and Conformational Analysis of Novel N(OCH₃)‐linked Disaccharide Analogues