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One-pot synthesis of high molecular weight synthetic heteroprotein dimers driven by charge complementarity electrostatic interactions.
- Source :
-
The Journal of organic chemistry [J Org Chem] 2014 Oct 17; Vol. 79 (20), pp. 9594-602. Date of Electronic Publication: 2014 Sep 30. - Publication Year :
- 2014
-
Abstract
- Despite the importance of protein dimers and dimerization in biology, the formation of protein dimers through synthetic covalent chemistry has not found widespread use. In the case of maleimide-cysteine-based dimerization of proteins, we show here that when the proteins have the same charge, dimerization appears to be inherently difficult with yields around 1% or less, regardless of the nature of the spacer used or whether homo- or heteroprotein dimers are targeted. In contrast, if the proteins have opposing (complementary) charges, the formation of heteroprotein dimers proceeds much more readily, and in the case of one high molecular weight (>80 kDa) synthetic dimer between cytochrome c and bovine serum albumin, a 30% yield of the purified, isolated dimer was achieved. This represents at least a 30-fold increase in yield for protein dimers formed from proteins with complementary charges, compared to when the proteins have the same charge, under otherwise similar conditions. These results illustrate the role of ionic supramolecular interactions in controlling the reactivity of proteins toward bis-functionalized spacers. The strategy here for effective synthetic dimerization of proteins could be very useful for developing novel approaches to study the important role of protein-protein interactions in chemical biology.
- Subjects :
- Animals
Biochemical Phenomena
Cattle
Cysteine chemistry
Cytochromes c chemistry
Dimerization
Models, Molecular
Molecular Weight
Protein Multimerization
Proteins chemistry
Serum Albumin chemistry
Static Electricity
Cytochromes c chemical synthesis
Proteins chemical synthesis
Serum Albumin chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1520-6904
- Volume :
- 79
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- The Journal of organic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 25231623
- Full Text :
- https://doi.org/10.1021/jo501713t