Removal of Acyl Protective Groups from Glycopeptides:  Base Does Not Epimerize Peptide Stereocenters, and β-Elimination Is Slow

Sjölin, Petter; Elofsson, Mikael; Kihlberg, Jan

doi:10.1021/jo951817r

Cited by 73 publications

(44 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…17,21 OGlcNAcylated peptides were synthesized using the protected Fmoc-Ser/Thr-(Ac 3 OGlcNAc)-OH, synthesized via a modification of the method of Arsequell, followed by initial peptide purification, O-deacetylation, and final peptide purification, yielding peptides site-specifically incorporating a single Ser or Thr OGlcNAc. 29,46,47 All peptides were examined by circular dichroism at 0.5 °C (Figures 3–12 and Table 1). Peptides were also examined by nuclear magnetic resonance (NMR) to determine residue-specific structural changes (Tables 2 and 3 and Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

OGlcNAcylation and Phosphorylation Have Similar Structural Effects in α-Helices: Post-Translational Modifications as Inducible Start and Stop Signals in α-Helices, with Greater Structural Effects on Threonine Modification

2014

View full text Add to dashboard Cite

OGlcNAcylation and phosphorylation are the major competing intracellular post-translational modifications of serine and threonine residues. The structural effects of both post-translational modifications on serine and threonine were examined within Baldwin model α-helical peptides (Ac-AKAAAAKAAAAKAAGY-NH2 or Ac-YGAKAAAAKAAAAKAA-NH2). At the N-terminus of an α-helix, both phosphorylation and OGlcNAcylation stabilized the α-helix relative to the free hydroxyls, with a larger induced structure for phosphorylation than for OGlcNAcylation, for the dianionic phosphate than for the monoanionic phosphate, and for modifications on threonine than for modifications on serine. Both phosphoserine and phosphothreonine resulted in peptides more α-helical than alanine at the N-terminus, with dianionic phosphothreonine the most α-helix-stabilizing residue here. In contrast, in the interior of the α-helix, both post-translational modifications were destabilizing with respect to the α-helix, with the greatest destabilization seen for threonine OGlcNAcylation at residue 5 and threonine phosphorylation at residue 10, with peptides containing either post-translational modification existing as random coils. At the C-terminus, both OGlcNAcylation and phosphorylation were destabilizing with respect to the α-helix, though the induced structural changes were less than in the interior of the α-helix. In general, the structural effects of modifications on threonine were greater than the effects on serine, because of both the lower α-helical propensity of Thr and the more defined induced structures upon modification of threonine than serine, suggesting threonine residues are particularly important loci for structural effects of post-translational modifications. The effects of serine and threonine post-translational modifications are analogous to the effects of proline on α-helices, with the effects of phosphothreonine being greater than those of proline throughout the α-helix. These results provide a basis for understanding the context-dependent structural effects of these competing protein post-translational modifications.

show abstract

Section: Resultsmentioning

confidence: 99%

OGlcNAcylation and Phosphorylation Have Similar Structural Effects in α-Helices: Post-Translational Modifications as Inducible Start and Stop Signals in α-Helices, with Greater Structural Effects on Threonine Modification

2014

View full text Add to dashboard Cite

show abstract

“…[15,19] Methods of glycopeptide synthesis that do not involve protected sugars do not require further manipulation of the sugar, which can lead to racemization of the amino acid. [20] Beyond affording N-glycosylated Asn and Gln building blocks, the functionalized phosphanes described herein could also be used to achieve traceless ligation of glycosyl azides to glycine, proline and the non-proteinogenic amino acid β-Ala. The resulting compounds are not meant to be incorporated into N-glycopeptide sequences, but can be used for the bioconjugation of carbohydrates to aglycons using chemically stable bonds and for the design of carbohydrate mimics which may resist in vivo to hydrolytic enzymes.…”

Section: Discussionmentioning

confidence: 99%

Stereoselective Synthesis of N‐Glycosyl Amino Acids by Traceless Staudinger Ligation of Unprotected Glycosyl Azides

2009

View full text Add to dashboard Cite

The stereoconservative Staudinger ligation of unprotectedα‐ and β‐glycosyl azides with 2‐(diphenylphosphanyl)‐4‐fluorophenyl esters to afford α‐ and β‐N‐glycosyl amino acids is described. The ligation method works reliably well for unprotected β‐azides of the gluco, galacto and fuco series. Lower yields (ca. 50 %) were obtained with a β‐glucosyl‐N‐acetyl azide. The reaction of an α‐glucosyl azide also led to major improvements compared with the use of non‐fluorinated phosphanes. All the N‐glycosyl amino acid products can be isolated and byproducts removed from the crude reaction mixtures by simple water extraction.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

show abstract

“…With the high sensitivity of O -sulfates to acid and the propensity of the glycopeptide to undergo base promoted β-elimination, 105–107 common amino acid side chain protective groups such as Boc and trityl should be avoided and the sequence and condition of deprotection need to be optimized.…”

Section: Resultsmentioning

confidence: 99%

Obstacles and solutions for chemical synthesis of syndecan-3 (53–62) glycopeptides with two heparan sulfate chains

Yang

Yoshida

Yang

et al. 2016

Carbohydrate Research

View full text Add to dashboard Cite

Proteoglycans play critical roles in many biological events. Due to their structural complexities, strategies towards synthesis of this class of glycopeptides bearing well-defined glycan chains are urgently needed. In this work, we give the full account of the synthesis of syndecan-3 glycopeptide (53–62) containing two different heparan sulfate chains. For assembly of glycans, a convergent 3+2+3 approach was developed producing two different octasaccharide amino acid cassettes, which were utilized towards syndecan-3 glycopeptides. The glycopeptides presented many obstacles for post-glycosylation manipulation, peptide elongation, and deprotection. Following screening of multiple synthetic sequences, a successful strategy was finally established by constructing partially deprotected single glycan chain containing glycopeptides first, followed by coupling of the glycan-bearing fragments and cleavage of the acyl protecting groups.

show abstract

Removal of Acyl Protective Groups from Glycopeptides: Base Does Not Epimerize Peptide Stereocenters, and β-Elimination Is Slow

Cited by 73 publications

References 23 publications

OGlcNAcylation and Phosphorylation Have Similar Structural Effects in α-Helices: Post-Translational Modifications as Inducible Start and Stop Signals in α-Helices, with Greater Structural Effects on Threonine Modification

OGlcNAcylation and Phosphorylation Have Similar Structural Effects in α-Helices: Post-Translational Modifications as Inducible Start and Stop Signals in α-Helices, with Greater Structural Effects on Threonine Modification

Stereoselective Synthesis of N‐Glycosyl Amino Acids by Traceless Staudinger Ligation of Unprotected Glycosyl Azides

Obstacles and solutions for chemical synthesis of syndecan-3 (53–62) glycopeptides with two heparan sulfate chains

Contact Info

Product

Resources

About