9 research outputs found
Design and synthesis of quasi-diastereomeric molecules with unchanging central, regenerating axial and switchable helical chirality via cleavage and formation of Ni(II)–O and Ni(II)–N coordination bonds
We describe herein the design and synthesis of asymmetric, pentadentate ligands, which are able to coordinate to Ni(II) cations leading to quasi-diastereomeric complexes displaying two new elements of chirality: stereogenic axis and helix along with configurational stabilization of the stereogenic center on the nitrogen. Due to the stereocongested structural characteristics of the corresponding Ni(II) complexes, the formation of quasi-diastereomeric products is highly stereoselective providing formation of only two, (Ra*,Mh*,Rc*) and (Ra*,Ph*,Rc*), out of the four possible stereochemical combinations. The reversible quasi-diastereomeric transformation between the products (Ra*,Mh*,Rc*) and (Ra*,Ph*,Rc*) occurs by intramolecular trans-coordination of Ni–NH and Ni–O bonds providing a basis for a chiral switch model
Efficient Synthesis of Sterically Constrained Symmetrically α,α-Disubstituted α-Amino Acids under Operationally Convenient Conditions
Michael Addition Reactions between Chiral Equivalents of a Nucleophilic Glycine and (S)- or (R)-3-[(E)-Enoyl]-4-phenyl-1, 3-oxazolidin-2-ones as a General Method for Efficient Preparation of b-Substituted Pyroglutamic Acids. Case of Topographically Controlled Stereoselectivity
Improved Synthesis of Proline-Derived Ni(II) Complexes of Glycine: Versatile Chiral Equivalents of Nucleophilic Glycine for General Asymmetric Synthesis of α-Amino Acids
Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia
Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of a surfactant-like substance in alveolar spaces and hypoxemic respiratory failure. Genetic PAP (GPAP) is caused by mutations in genes encoding surfactant proteins or genes encoding a surfactant phospholipid transporter in alveolar type II epithelial cells. GPAP is also caused by mutations in genes whose products are implicated in surfactant catabolism in alveolar macrophages (AMs). We performed whole-exome sequence analysis in a family affected by infantile-onset PAP with hypogammaglobulinemia without causative mutations in genes associated with PAP: SFTPB, SFTPC, ABCA3, CSF2RA, CSF2RB, and GATA2. We identified a heterozygous missense variation in OAS1, encoding 2',5'-oligoadenylate synthetase 1 (OAS1) in three affected siblings, but not in unaffected family members. Deep sequence analysis with next-generation sequencing indicated 3.81% mosaicism of this variant in DNA from their mother's peripheral blood leukocytes, suggesting that PAP observed in this family could be inherited as an autosomal-dominant trait from the mother. We identified two additional de novo heterozygous missense variations of OAS1 in two unrelated simplex individuals also manifesting infantile-onset PAP with hypogammaglobulinemia. PAP in the two simplex individuals resolved after hematopoietic stem cell transplantation, indicating that OAS1 dysfunction is associated with impaired surfactant catabolism due to the defects in AMs