211869-78-2Relevant articles and documents
First total synthesis of a GPI-anchored peptide
Xue, Jie,Shao, Ning,Guo, Zhongwu
, p. 4020 - 4029 (2007/10/03)
A GPI-anchored dipeptide of sperm CD52 antigen was prepared through a convergent synthesis. First, the dipeptide with its C-terminus free and the GPI with its nonreducing end phosphoeth-anolamine bearing a free amino group were synthesized separately. Then, the two building blocks were coupled with use of EDC/HOBt as the condensation reagent. Finally, the GPI-anchored peptide was deprotected to give the target molecule 1.
Convergent synthesis of an inner core GPI of sperm CD52
Xue, Jie,Guo, Zhongwu
, p. 2015 - 2018 (2007/10/03)
An inner core of the GPI anchor of sperm CD52 antigens was synthesized by a highly convergent process using specially modified inositol, glucosamine and phospholipid as key building blocks. This paper also presents a new and efficient procedure to prepare
Synthesis of the fully phosphorylated GPI anchor pseudohexasaccharide of Toxoplasma gondii
Pekari,Tailler,Weingart,Schmidt
, p. 7432 - 7442 (2007/10/03)
Retrosynthesis of the fully phosphorylated glycosylphosphatidyl inositol (GPI) anchor pseudohexasaccharide 1a led to building blocks 2-6, of which 5 and 6 are known. The formation of pseudodisaccharide building block 2 is based on readily available building block 7, which gave, via derivative 11 and its glycosylation with known donor 12, the desired compound 2. Building block 3, with the required access to all hydroxy groups being permitted, was prepared from mannose in five steps. From a readily available precursor, building block 4 was obtained, which on reaction with 3 gave disaccharide 23. The synthesis of the decisive pseudohexasaccharide intermediate 32 was based on the reaction of 23 with 5, then with 6, and finally with 2. To obtain high stereoselectivity and good yields in the glycosylation reactions, anchimeric assistance was employed. To enable regioselective attachment of the two different phosphorus esters, the 6f-O-silyl group of 32 was first removed and the aminoethyl phosphate residue was attached. Then the MPM group was oxidatively removed, and the second phosphate residue was introduced. Unprotected 1a was then liberated in two steps: treatment with sodium methanolate removed the acetyl protecting groups, and finally, catalytic hydrogenation afforded the desired target molecule, which could be fully structurally assigned.
Molecular Recognition at the Phosphatidylinositol 3,4,5-Trisphosphate-Binding Site. Studies Using the Permuted Isomers of Phosphatidylinositol Trisphosphate
Wang, Da-Sheng,Hsu, Ao-Lin,Song, Xueqin,Chiou, Chi-Ming,Chen, Ching-Shih
, p. 5430 - 5437 (2007/10/03)
Permuted isomers of L-α-phosphatidyl-D-myo-inositol trisphosphate (PtdInsP3), including PtdIns(3,4,5)P3, PtdIns(3,4,6)P3, PtdIns(3,5,6)P3, and PtdIns(4,5,6)P3, have been synthesized as part of our effort to understand the underlying principles governing ligand selection for PtdIns(3,4,5)P3-specific binding proteins. These PtdInsP3 isomers are examined by using two PtdIns(3,4,5)P3-dependent functional assays: binding to the C-terminal SH2 domain of the p85 regulatory subunit of PI 3-kinase and platelet aggregation. Our data show that all these isomers bind to the SH2 domain with comparable affinity despite variation in the regioisomeric distribution of phosphate functions. Moreover, all these phospholipids are capable of triggering platelet aggregation with the relative potency of PtdIns(3,4,5)P3 > PtdIns(3,5,6)P3 > PtdIns(4,5,6)P3 > PtdIns(3,4,6)P3. Evidence suggests that these PtdInsP3's facilitate cell aggregation by activating Ca2+ influx across the plasma membrane. In contrast, other inositol lipids examined including PtdIns(3,4)P2, PtdIns(4,5)P2, PtdIns(3)P, and PtdIns(4)P are ineffective in eliciting the aggregation even at much higher concentrations. Taken together, the present data suggest that the charge density on the phosphorylated inositol ring represents a key factor in determining the phosphoinositide binding specificity of target proteins. It is conceivable that the interaction with the PtdIns(3,4,5)P3-binding motif requires the participation of all three phosphates on the headgroup of PtdIns(3,4,5)P3. Consequently, other membrane phosphoinositides (e.g., the bis- and monophosphates) become thermodynamically unfavorable for the binding to these PtdIns(3,4,5)P3 targets.
