Linked Life Data

15579079

Source:http://linkedlifedata.com/resource/pubmed/id/15579079

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
31
pubmed:dateCreated
2004-12-6
pubmed:abstractText
Biological activity and clinical efficacy of a therapeutic protein are contingent upon the structural stability, bioavailability, and clearance rates of the protein. In this review, we examine the class of 4-helical bundle cytokines for common stability properties that may affect biological structure and efficacy. Three critical stability features that are hallmarks of this class of cytokines are the pH dependence of structural stability, the presence of folding intermediates, and the population of aggregation intermediates. We hypothesize that certain cytokines have increased stability in acid to enable receptor-mediated clearance, and that reengineering local endocytic trafficking can result in dramatic improvements in global serum half-life and therapeutic efficacy. The common feature of folding and aggregation intermediates has implications on kinetic folding pathways, membrane permeability, solubility, and precipitation properties that are critical for commercial production, formulation, and delivery. Understanding the structural stability properties of this class of cytokines may help elucidate new approaches to improving therapeutic efficacy.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1381-6128
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3901-11
pubmed:dateRevised
2006-2-27
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Common structural stability properties of 4-helical bundle cytokines: possible physiological and pharmaceutical consequences.
pubmed:affiliation
Pharmaceutics Department, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA. mspeed@amgen.com
pubmed:publicationType
Journal Article, Review