Abstract
Molecular superglues covalently ligate two or more macromolecules together into super stable, covalently linked assemblies. The discovery of intramolecular isopeptide and ester bond crosslinks in bacterial adhesin proteins, inspired the development of two distinct protein ligating technologies based on split protein domains. These chemically distinct technologies could be combined as orthogonal (non-cross-reacting) technologies to make complex assemblies. Here we provide simple practical instructions in the discovery, characterisation, and application of orthogonal ester bond crosslinks as molecular superglues. A large toolkit of diverse, orthogonal molecular superglues will expand our assembly repertoire, and afford increasingly more complex one-, two-, and three-dimensional protein nanomaterials with exquisite control over the final molecular architecture.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Kang HJ, Coulibaly F, Clow F, Proft T, Baker EN (2007) Science 318:1625
Kwon H, Squire CJ, Young PG, Baker EN (2014) Proc Natl Acad Sci U S A 111:1367
Zakeri B, Howarth M (2010) J Am Chem Soc 132:4526
Young PG, Yosaatmadja Y, Harris PW, Leung IK, Baker EN, Squire CJ (2017) Harnessing ester bond chemistry for protein ligation. Chem Commun (Camb) 53(9):1502–1505
Schoene C, Fierer JO, Bennett SP, Howarth M (2014) Angew Chem Int Ed 53:6101
Sun F, Zhang WB, Mahdavi A, Arnold FH, Tirrell DA (2014) Proc Natl Acad Sci U S A 111:11269
Thrane S, Janitzek CM, Matondo S, Resende M, Gustavsson T, de Jongh WA, Clemmensen S, Roeffen W, van de Vegte-Bolmer M, van Gemert GJ, Sauerwein R, Schiller JT, Nielsen MA, Theander TG, Salanti A, Sander AF (2016) J Nanobiotechnol 14:30
Fierer JO, Veggiani G, Howarth M (2014) Proc Natl Acad Sci U S A 111:E1176
Veggiani G, Nakamura T, Brenner MD, Gayet RV, Yan J, Robinson CV, Howarth M (2016) Proc Natl Acad Sci U S A 113:1202
Tan LL, Hoon SS, Wong FT (2016) PLoS One 11:e0165074
Acknowledgments
We would like to acknowledge William Bramley, Robbie Kerridge, and Yuliana Yosaatmadja for their work in developing the ester bond ligation technology.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Young, P.G., Squire, C.J. (2020). Molecular Superglues: Discovery and Engineering Orthogonalization. In: Gerrard, J., Domigan, L. (eds) Protein Nanotechnology. Methods in Molecular Biology, vol 2073. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9869-2_6
Download citation
DOI: https://doi.org/10.1007/978-1-4939-9869-2_6
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-4939-9868-5
Online ISBN: 978-1-4939-9869-2
eBook Packages: Springer Protocols