134262-54-7Relevant academic research and scientific papers
Chemical Synthesis of a Glycopeptide Derived from Skp1 for Probing Protein Specific Glycosylation
Chinoy, Zoeisha S.,Schafer, Christopher M.,West, Christopher M.,Boons, Geert-Jan
, p. 11779 - 11787 (2015)
Skp1 is a cytoplasmic and nuclear protein, best known as an adaptor of the SCF family of E3-ubiquitin ligases that label proteins for their degradation. Skp1 in Dictyostelium is posttranslationally modified on a specific hydroxyproline (Hyp) residue by a pentasaccharide, which consists of a Fucα1,2-Galβ-1,3-GlcNAcα core, decorated with two α-linked Gal residues. A glycopeptide derived form Skp1 was prepared to characterize the α-galactosyltransferase (AgtA) that mediates the addition of the α-Gal moieties, and to develop antibodies suitable for tracking the trisaccharide isoform of Skp1 in cells. A strategy was developed for the synthesis of the core trisaccharide-Hyp based on the use of 2-naphthylmethyl (Nap) ethers as permanent protecting groups to allow late stage installation of the Hyp moiety. Tuning of glycosyl donor and acceptor reactivities was critical for achieving high yields and anomeric selectivities of glycosylations. The trisaccharide-Hyp moiety was employed for the preparation of the glycopeptide using microwave-assisted solid phase peptide synthesis. Enzyme kinetic studies revealed that trisaccharide-Hyp and trisaccharide-peptide are poorly recognized by AgtA, indicating the importance of context provided by the native Skp1 protein for engagement with the active site. The trisaccharide-peptide was a potent immunogen capable of generating a rabbit antiserum that was highly selective toward the trisaccharide isoform of full-length Skp1. Antibody tracking: A glycopeptide containing a trisaccharide-hydroxyproline moiety was synthesized to characterize the substrate requirements of α-galactosyltransferase (AgtA) that mediates the addition of the α-Gal residues to the glycan of the glycoprotein Skp1 and to develop antibodies suitable for tracking the trisaccharide isoform of Skp1 in cells.
Catalysis with phosphine-containing amino acids in various "turn" motifs
Agarkov, Anton,Greenfield, Scott J.,Ohishi, Takahiro,Collibee, Scott E.,Gilbertson, Scott R.
, p. 8077 - 8085 (2007/10/03)
We have been actively involved in the development of parallel approaches for the discovery of phosphine ligands. Our approach has been based on the incorporation of phosphine-containing amino acids into peptide sequences that are designed to have stable secondary structures. We have examined helical and turn secondary structures and have reported that alkylation of cyclopentenyl acetate with dimethylmalonate can be catalyzed in high enantiomeric excess (ee) with a β-turn-based ligand. The importance of the peptide secondary structure was demonstrated through the synthesis of a series of peptide ligands where the nature of the turn-forming residues was probed. Additionally, other turn-forming units and a variety of different phosphine-containing amino acids have been examined for their ability to control the selectivity of the allylation reaction. This paper reports the results obtained through the examination of different turn motifs as well as different phosphine substitutions on the "best" turn sequence, Pps-Pro-D-Xxx-Pps.
