01631nas a2200181   4500008004100000022001400041245010800055210006900163260007100232300001200303490000600315520092400321100001601245700002001261700002001281700002201301856012601323       2016                        eng d  a2161-165300aControlled synthesis of end-functionalized mannose-6-phosphate glycopolypeptides for lysosome targeting0 aControlled synthesis of endfunctionalized mannose6phosphate glyc  a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcJUL  a809-8130 v53 a<p>The ubiquitous expression of the mannose-6-phosphate receptor on the majority of human cells makes it a valid target in the quest to deliver therapeutics selectively to the lysosome. In this work end-functionalized polyvalent mannose-6-phosphate glycopolypeptides (M6P-GPs) with high molecular weights (up to 22 kDa) have been synthesized via NCA polymerization. These synthetic M6P-GPs were found to display minimal toxicity to cells in vitro and show exceptional selectivity for trafficking into lysosomes in various cell lines. Comparison of the cellular uptake behavior of M6P-GP and the corresponding mannose-GP polymer reveals that incorporation of the phosphate moiety at the 6-position of mannose completely alters its trafficking behavior and becomes exclusively lysosome specific. We also demonstrate that trafficking of M6P-GPs in mammalian cells is likely associated with the CI-MPR receptor pathway.</p>1 aDas, Soumen1 aParekh, Nimisha1 aMondal, Basudeb1 aGupta, Sayam, Sen  uhttps://library.ncl.res.in/content/controlled-synthesis-end-functionalized-mannose-6-phosphate-glycopolypeptides-lysosome