Tumour targeting: biological factors and formulation advances in injectable lipid nanoparticles.

Cancer chemotherapeutic agents are often administered systemically. Following systemic administration, numerous biological factors associated with the tumours influence the delivery of the drugs to the tumours. These factors have been extensively studied for the last 2 decades.

Processing enzyme glucosidase II: proposed catalytic residues and developmental regulation during the ontogeny of the mouse mammary gland.

Following the action of glucosidase I to clip the terminal alpha1,2-linked glucose, glucosidase II sequentially cleaves the two inner alpha1,3-linked glucose residues from the Glcalpha1,2Glcalpha1,3Glcalpha1,3Man(9)GlcNAc(2) oligosaccharide of the incipient glycoprotein as it undergoes folding and maturation. Glucosidase II belongs to family 31 glycosidases. These enzymes act by the acid-base catalytic mechanism.

Synthesis of a novel photoaffinity derivative of 1-deoxynojirimycin for active site-directed labeling of glucosidase I.

Glucosidase I releases the distal alpha1,2-glucosyl residue in the Glc(3)Man(9)GlcNAc(2) precursor immediately after its transfer from the dolichol-P-P-linked intermediate in the endoplasmic reticulum and triggers the processes for the posttranslational remodeling, folding, and maturation of N-linked glycoproteins. The enzyme has been purified and characterized from several eukaryotic systems. Its cDNA and the gene have also been cloned.

STAT5a regulates the GlcNAc-1-phosphate transferase gene transcription and expression.

The dolichyl-phosphate alpha-N-acetylglucosaminephosphotransferase 2 (Dpagt2) gene in the mouse has a housekeeping promoter, and its expression is regulated during the development and hormonally modulated lactogenesis of the mammary gland. Previous studies showed that the transcription of the mouse mammary Dpagt2 gene is stimulated by the lactogenic hormones, insulin, glucocorticoid receptor (GR), and prolactin. Transcription factors which bind to the Dpagt2 gene promoter region can influence the expression level of the Dpagt2 gene.

Developmental and hormonal regulation of protein N-glycosylation in the mammary gland.

Glycosylation represents the most common conjugation of both membrane-bound and secreted proteins of animal cells. Among the different types of glycosylation, the N-linked attachment of sugars to the polypeptide backbone is by far the most abundant modification. The biosynthesis of the precursor carbohydrate unit of these proteins is initiated by a stepwise assembly of Glc3Man9GlcNAc2P-P-Dol in the dolichol cycle, its transfer en bloc to the nascent polypeptide in the rough endoplasmic reticulum (RER), followed by excision of the glucosyl residues by processing-specific enzymes, glucosidase I and II, also resident in the endoplasmic reticulum.