Protein Complexation and pH Dependent Release Using Boronic Acid Containing PEG-Polypeptide Copolymers.
New poly(L-lysine)-b-poly(ethylene glycol) copolypeptides have been prepared, where the side-chain amine groups of lysine residues are modified to contain ortho-amine substituted phenylboronic acid, i.e., Wulff-type phenylboronic acid (WBA), groups to improve their pH responsive, carbohydrate binding properties. These block copolymers form nanoscale complexes with glycosylated proteins that are stable at physiological pH, yet dissociate and release the glycoproteins under acidic conditions, similar to those found in endosomal and lysosomal compartments within cells. These results suggest that WBA modified polypeptide copolymers are promising for further development as degradable carriers for intracellular protein delivery.
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E Young Dr. E, Los Angeles, CA, 90095-1600, USA.
Graciela E
GE
Negri
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E Young Dr. E, Los Angeles, CA, 90095-1600, USA.|Department of Bioengineering, University of California, Los Angeles, 5121 Engineering 5, Los Angeles, CA, 90095-1600, USA.
Timothy J
TJ
Deming
D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D016227:Benzoquinones / Q000494:pharmacology / Q000627:therapeutic use; D001897:Boronic Acids / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D004338:Drug Combinations; D005260:Female; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D047029:Lactams, Macrocyclic / Q000494:pharmacology / Q000627:therapeutic use; D008819:Mice, Nude; D008823:Micelles; D009336:Necrosis; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use; D010455:Peptides / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D016227:Benzoquinones; D001897:Boronic Acids; D004338:Drug Combinations; D019394:Ki-67 Antigen; D047029:Lactams, Macrocyclic; D008823:Micelles; D010455:Peptides; D011091:Polyesters; D011108:Polymers; D011506:Proteins; C578609:triolimus; D011092:Polyethylene Glycols; C033616:poly(lactide); D051057:Proto-Oncogene Proteins c-akt; D017239:Paclitaxel; D020123:Sirolimus
block copolymer; boronic acid; polypeptide; protein delivery