Intrinsic bioconjugation for site-specific protein PEGylation at N-terminal serine.

نویسندگان

  • Paul M Levine
  • Timothy W Craven
  • Richard Bonneau
  • Kent Kirshenbaum
چکیده

Recently developed chemical ligation protocols were elaborated for rapid N-terminal protein PEGylation. We introduce a PEG-salicylaldehyde ester and demonstrate its site-specific ligation to the N-terminus of the RNase S protein and to the therapeutic polypeptide PTH (1-34).

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Site – specific PEGylation of rHuEPO and evaluation of its biological activity and stability

Despite the critical role of erythropoietin (EPO) as therapeutic agent in treatment of anemia, its consumption is limited due to several disadvantages including the product short half-life, immunogenicity and susceptibility to proteolytic degradation. To overcome these drawbacks efficient methods such as site-specific PEGylation have been developed among witch N-terminal PEGylation has found mo...

متن کامل

Site-Specific PEGylation of Recombinant Immunotoxin DAB389IL-2: Structural and Functional Assessment

Background: DAB389IL-2 is considered a fusion immunotoxin and it is used for the CTCL therapy. DAB389IL-2 includes of two distinct portions; the catalytic domain of diphtheria toxin and IL-2. DAB389IL-2 duo to the presence of a free cysteine residue (Cys 513 in IL-2 part) is prone to unwanted intramolecular and intermolecular disulfide bonds formation and aggregation problems. Aggregation is co...

متن کامل

Site-specific PEGylation at histidine tags.

The efficacy of protein-based medicines can be compromised by their rapid clearance from the blood circulatory system. Achieving optimal pharmacokinetics is a key requirement for the successful development of safe protein-based medicines. Protein PEGylation is a clinically proven strategy to increase the circulation half-life of protein-based medicines. One limitation of PEGylation is that ther...

متن کامل

Design, cloning, expression and evaluation of cysteine-substitutes of intact and truncated molecules of streptokinase

Introduction: Thrombosis and the blockage of blood vessels with clots, can lead to acute myocardial infarction and some times even death. Aside from surgical interventions to remove the blockage, the only available treatment is the administration of thrombolytic agents to dissolve the blood clot. Streptokinase (SK) is the most commonly used fibrinolytic drug for this purpose. However, SK...

متن کامل

Stabilization of bacterially expressed erythropoietin by single site-specific introduction of short branched PEG chains at naturally occurring glycosylation sites.

The covalent attachment of polyethylene glycol (PEG) to therapeutic proteins can improve their physicochemical properties. In this work we utilized the non-natural amino acid p-azidophenylalanine (pAzF) in combination with the chemoselective Staudinger-phosphite reaction to install branched PEG chains to recombinant unglycosylated erythropoietin (EPO) at each single naturally occurring glycosyl...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Chemical communications

دوره 50 52  شماره 

صفحات  -

تاریخ انتشار 2014