NDLI: Molecular Insight into the Steric Shielding Effect of PEG on the Conjugated Staphylokinase: Biochemical Characterization and Molecular Dynamics Simulation

Content Provider	PubMed Central
Author	Mu, Qimeng Hu, Tao Yu, Jingkai
Editor	Verma, Chandra
Copyright Year	2013
Abstract	PEGylation is a successful approach to improve potency of a therapeutic protein. The improved therapeutic potency is mainly due to the steric shielding effect of PEG. However, the underlying mechanism of this effect on the protein is not well understood, especially on the protein interaction with its high molecular weight substrate or receptor. Here, experimental study and molecular dynamics simulation were used to provide molecular insight into the interaction between the PEGylated protein and its receptor. Staphylokinase (Sak), a therapeutic protein for coronary thrombolysis, was used as a model protein. Four PEGylated Saks were prepared by site-specific conjugation of 5 kDa/20 kDa PEG to N-terminus and C-terminus of Sak, respectively. Experimental study suggests that the native conformation of Sak is essentially not altered by PEGylation. In contrast, the bioactivity, the hydrodynamic volume and the molecular symmetric shape of the PEGylated Sak are altered and dependent on the PEG chain length and the PEGylation site. Molecular modeling of the PEGylated Saks suggests that the PEG chain remains highly flexible and can form a distinctive hydrated layer, thereby resulting in the steric shielding effect of PEG. Docking analyses indicate that the binding affinity of Sak to its receptor is dependent on the PEG chain length and the PEGylation site. Computational simulation results explain experimental data well. Our present study clarifies molecular details of PEG chain on protein surface and may be essential to the rational design, fabrication and clinical application of PEGylated proteins.
Related Links	http://dx.doi.org/10.1371/journal.pone.0068559
Starting Page	68559
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	7
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-07-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Insight into the Stability of Cross-β Amyloid Fibril from VEALYL Short Peptide with Molecular Dynamics Simulation

Correction: CONSTRICTOR: Constraint Modification Provides Insight into Design of Biochemical Networks

Insight into the Structure, Dynamics and the Unfolding Property of Amylosucrases: Implications of Rational Engineering on Thermostability

Proteomic Insight into the Molecular Function of the Vitreous

PSMA Ligand Conjugated PCL-PEG Polymeric Micelles Targeted to Prostate Cancer Cells

Insight Derived from Molecular Dynamics Simulations into Molecular Motions, Thermodynamics and Kinetics of HIV-1 gp120

Mapping the Conformational Dynamics and Pathways of Spontaneous Steric Zipper Peptide Oligomerization

Genome Digging: Insight into the Mitochondrial Genome of Homo

Structural Insight into the Clostridium difficile Ethanolamine Utilisation Microcompartment

Molecular Insight into the Steric Shielding Effect of PEG on the Conjugated Staphylokinase: Biochemical Characterization and Molecular Dynamics Simulation

Similar Documents

Insight into the Stability of Cross-β Amyloid Fibril from VEALYL Short Peptide with Molecular Dynamics Simulation

Correction: CONSTRICTOR: Constraint Modification Provides Insight into Design of Biochemical Networks

Insight into the Structure, Dynamics and the Unfolding Property of Amylosucrases: Implications of Rational Engineering on Thermostability

Proteomic Insight into the Molecular Function of the Vitreous

PSMA Ligand Conjugated PCL-PEG Polymeric Micelles Targeted to Prostate Cancer Cells

Insight Derived from Molecular Dynamics Simulations into Molecular Motions, Thermodynamics and Kinetics of HIV-1 gp120

Mapping the Conformational Dynamics and Pathways of Spontaneous Steric Zipper Peptide Oligomerization

Genome Digging: Insight into the Mitochondrial Genome of Homo

Structural Insight into the Clostridium difficile Ethanolamine Utilisation Microcompartment

Molecular Insight into the Steric Shielding Effect of PEG on the Conjugated Staphylokinase: Biochemical Characterization and Molecular Dynamics Simulation