Document Detail


Mass spectrometry-guided optimization and characterization of a biologically active transferrin-lysozyme model drug conjugate.
MedLine Citation:
PMID:  23534953     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transferrin is a promising drug carrier that has the potential to deliver metals, small organic molecules and therapeutic proteins to cancer cells and/or across physiological barriers (such as the blood-brain barrier). Despite this promise, very few transferrin-based therapeutics have been developed and reached clinical trials. This modest success record can be explained by the complexity and heterogeneity of protein conjugation products, which also pose great challenges to their analytical characterization. In this work, we use lysozyme conjugated to transferrin as a model therapeutic that targets the central nervous system (where its bacteriostatic properties may be exploited to control infection) and develop analytical protocols based on electrospray ionization mass spectrometry to characterize its structure and interactions with therapeutic targets and physiological partners critical for its successful delivery. Mass spectrometry has already become an indispensable tool facilitating all stages of the protein drug development process, and this work demonstrates the enormous potential of this technique in facilitating the development of a range of therapeutically effective protein-drug conjugates.
Authors:
Son N Nguyen; Cedric E Bobst; Igor A Kaltashov
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-04-10
Journal Detail:
Title:  Molecular pharmaceutics     Volume:  10     ISSN:  1543-8392     ISO Abbreviation:  Mol. Pharm.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-06     Completed Date:  2013-12-16     Revised Date:  2014-05-08    
Medline Journal Info:
Nlm Unique ID:  101197791     Medline TA:  Mol Pharm     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1998-2007     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Anti-Bacterial Agents / administration & dosage,  chemistry
Anti-Infective Agents / administration & dosage,  chemistry
Central Nervous System Agents / administration & dosage,  chemistry
Chemistry, Pharmaceutical
Drug Carriers / chemistry*
Humans
Micrococcus / drug effects
Molecular Structure
Muramidase / administration & dosage,  chemistry*,  metabolism
Protein Binding
Receptors, Transferrin / metabolism
Spectrometry, Mass, Electrospray Ionization
Transferrin / administration & dosage,  chemistry*,  metabolism
Grant Support
ID/Acronym/Agency:
R01 GM061666/GM/NIGMS NIH HHS; R01 GM061666/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Anti-Infective Agents; 0/Central Nervous System Agents; 0/Drug Carriers; 0/Receptors, Transferrin; 0/Transferrin; EC 3.2.1.17/Muramidase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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