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One-Pot synthesis of high molecular weight synthetic heteroprotein dimers driven by charge complementarity electrostatic interactions

One-Pot synthesis of high molecular weight synthetic heteroprotein dimers driven by charge complementarity electrostatic interactions
One-Pot synthesis of high molecular weight synthetic heteroprotein dimers driven by charge complementarity electrostatic interactions
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.
0022-3263
9594-9602
Hvasanov, David
23df8910-ea97-465b-8fdc-e839f70e39c0
Nam, Ekaterina V.
5e322bec-b6d2-4e96-9cb2-efe555e6f229
Peterson, Joshua R.
892e72ef-0596-4779-af06-ee61f1af2e16
Pornsaksit, Dithepon
20b0722a-1506-4e99-ace5-16d8b2148a26
Wiedenmann, Jörg
ad445af2-680f-4927-90b3-589ac9d538f7
Marquis, Christopher P.
c60a5b09-5b79-412d-afd8-b93998c445c2
Thordarson, Pall
9d3b961d-c277-46ca-9eef-1bc77133fb94
Hvasanov, David
23df8910-ea97-465b-8fdc-e839f70e39c0
Nam, Ekaterina V.
5e322bec-b6d2-4e96-9cb2-efe555e6f229
Peterson, Joshua R.
892e72ef-0596-4779-af06-ee61f1af2e16
Pornsaksit, Dithepon
20b0722a-1506-4e99-ace5-16d8b2148a26
Wiedenmann, Jörg
ad445af2-680f-4927-90b3-589ac9d538f7
Marquis, Christopher P.
c60a5b09-5b79-412d-afd8-b93998c445c2
Thordarson, Pall
9d3b961d-c277-46ca-9eef-1bc77133fb94

Hvasanov, David, Nam, Ekaterina V., Peterson, Joshua R., Pornsaksit, Dithepon, Wiedenmann, Jörg, Marquis, Christopher P. and Thordarson, Pall (2014) One-Pot synthesis of high molecular weight synthetic heteroprotein dimers driven by charge complementarity electrostatic interactions. Journal of Organic Chemistry, 79 (20), 9594-9602. (doi:10.1021/jo501713t).

Record type: Article

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.

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Published date: October 2014
Organisations: Ocean and Earth Science

Identifiers

Local EPrints ID: 372413
URI: http://eprints.soton.ac.uk/id/eprint/372413
ISSN: 0022-3263
PURE UUID: 955b2142-7d70-441d-ba1c-4297e23abb3f
ORCID for Jörg Wiedenmann: ORCID iD orcid.org/0000-0003-2128-2943

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Date deposited: 03 Dec 2014 11:21
Last modified: 03 Dec 2019 01:45

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