| Multivalency of Sonic hedgehog conjugated to linear polymer chains modulates protein potency. | |
| | |
MedLine Citation:
|
PMID: 18380472 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
A potently active multivalent form of the protein Sonic hedgehog (Shh) was produced by bioconjugation of a modified recombinant form of Shh to the linear polymers poly(acrylic acid) (pAAc) and hyaluronic acid (HyA) via a two-step reaction exploiting carboimiide and maleimide chemistry. Efficiency of the conjugation was approximately 75% even at stoichiometric ratios of 30 Shh molecules per linear HyA chain (i.e., 30:1 Shh/HyA). Bioactivity of the conjugates was tested via a cellular assay across a range of stoichiometric ratios of Shh molecules to HyA linear chains, which was varied from 0.6:1 Shh/HyA to 22:1 Shh/HyA. Results indicate that low conjugation ratios decrease Shh bioactivity and high ratios increase this activity beyond the potency of monomeric Shh, with approximately equal activity between monomeric soluble Shh and conjugated Shh at 7:1 Shh/HyA. In addition, high-ratio constructs increased angiogenesis determined by the in vivo chick chorioallantoic membrane (CAM) assay. These results are captured by a kinetic model of multiple interactions between the Shh/HyA conjugates and cell surface receptors resulting in higher cell signaling at lower bulk Shh concentrations. |
| | |
Authors:
|
Samuel T Wall; Krishanu Saha; Randolph S Ashton; Kimberly R Kam; David V Schaffer; Kevin E Healy |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2008-04-02 |
Journal Detail:
|
Title: Bioconjugate chemistry Volume: 19 ISSN: 1520-4812 ISO Abbreviation: Bioconjug. Chem. Publication Date: 2008 Apr |
Date Detail:
|
Created Date: 2008-04-16 Completed Date: 2008-07-28 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9010319 Medline TA: Bioconjug Chem Country: United States |
Other Details:
|
Languages: eng Pagination: 806-12 Citation Subset: IM |
Affiliation:
|
Department of Bioengineering, University of California, Berkeley, California 94720-1760, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Angiogenesis Inducing Agents
/
metabolism Animals Chorioallantoic Membrane / blood supply Hedgehog Proteins / metabolism* Kinetics Models, Biological Neovascularization, Physiologic Polymers / metabolism* |
| Chemical | |
Reg. No./Substance:
|
0/Angiogenesis Inducing Agents; 0/Hedgehog Proteins; 0/Polymers |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Long functionalized poly(ethylene glycol)s of defined molecular weight: synthesis and application in...
Next Document: Predominant release of lysosomal enzymes by newborn rat microglia after LPS treatment revealed by pr...