title: Enhanced stability and therapeutic utility of proteins upon conjugation with hydrophilic polymers.
abstract: The Pharmacological utility of various exogenous proteins is considerably impeded, since upon infusion, they are liable to rapid systemic clearance, proteolysis, in addition to eliciting severe immunological reactions. Upon conjugation with hydrophilic polymers like polyethylene glycol and dextran, the altered topology of proteins, often hinders interaction with their corresponding complementary surfaces. This is manifest in their increased circulatory-lives, as a fall out of decreased binding to proteases, pre-existing antibodies and other opsonins that mediate clearance by the reticuloendothelial-system as well as receptors mediating specific organ uptake. Further, an increase in conjugate size beyond the threshold limit of 70 kDa, permits small proteins to escape clearance via renal filtration. Upon covalent modification, proteins are generally endowed with an intrinsic inertness which is reflected in their enhanced stability in extremes of pH and temperature, presence of proteases and other denaturing conditions. The enhanced intracellular stability of conjugates which may also be responsible for their altered immunological properties is likely to be a consequence of the changed physiochemical properties of the conjugates. The therapeutic efficacy of these conjugates in clinical trials indicate their tremendous utility in pharmacological procedures.
authors.affiliation: Department of Biochemistry, University of Delhi South Campus, India.
authors.forename: G
authors.initials: G
authors.lastname: Mitra
authors.forename: S
authors.initials: S
authors.lastname: Mumtaz
authors.forename: B K
authors.initials: BK
authors.lastname: Bachhawat
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004355:Drug Stability; D011108:Polymers / Q000737:chemistry* / Q000627:therapeutic use; D011506:Proteins / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D011108:Polymers; D011506:Proteins