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Ubertino

09/18/14 11:58 AM

#99167 RE: Ubertino #98919

In re mannose-binding lectin

United States Patent 8,173,764
Diwan , et al. May 8, 2012

Solubilization and targeted delivery of drugs with self-assembling amphiphilic polymers


Exemplary cell-targeting moieties include but are not limited to receptor-specific ligands, antibodies, and other targeting moieties, such as peptides possessing an Arginine-Glycine-Aspartic acid (RGD) amino acid sequence or a Tyrosine-Isoleucine-Serine-Arginine-Glycine (YISRG) motif; growth factors including epidermal growth factor, vascular endothelial growth factor and fibroblast growth factor; viral surface ligands such as sialic acid and N-acetylneuraminic acid derivatives; cell receptor ligands such as folate, methotrexate, pteroic acid, estradiol, estratriol, testosternone, and other hormones; mannose-6-phosphate, sugars, vitamins, tryptophan, and the like. Antibodies are preferably monoclonal antibodies directed at cell-specific surface antigens; suitable targeting moieties include not only complete antibodies but also antibody fragments containing the active antigen-binding sequences, such as Fab'2 fragments, Fab' fragments, or short chain peptide analogues of the active antigen binding sequences of such antibodies.



LINK

Mannose 6-phosphate
From Wikipedia, the free encyclopedia

Mannose-6-phosphate (M6P) is a molecule bound by lectin in the immune system. M6P is converted to fructose 6-phosphate by mannose phosphate isomerase.

M6P is a key targeting signal for acid hydrolase precursor proteins that are destined for transport to lysosomes. The M6P tag is added to such proteins in the cis-Golgi apparatus. Specifically, in a reaction involving uridine diphosphate (UDP) and N-acetylglucosamine, the enzyme N-acetylglucosamine-1-phosphate transferase catalyzes the N-linked glycosylation of asparagine residues with M6P. Once appropriately marked with the M6P targeting signal, these proteins are moved to the trans-Golgi network. There, the M6P moiety is recognized and bound by mannose 6-phosphate receptor (MPR) proteins at pH 6.5-6.7.[1]

The M6P-tagged lysosomal enzymes are shipped to the late endosomes via vesicular transport.[1] The pH in the late endosome can reach 6.0, which causes dissociation of M6P from its receptor.[1] Upon release, the enzymes are ferried to their final destination in the lysosomes.[1] The MPRs are packed into vesicles that bud off the late endosome and return to the "trans"-Golgi network.[1] In this way, the MPRs can be recycled.
http://en.wikipedia.org/wiki/Mannose_6-phosphate

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