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Noncovalent synthesis of protein dendrimers

Title: Noncovalent synthesis of protein dendrimers
Authors: Lempens, EHM Edith; Baal, I Ingrid van; Dongen, JLJ Joost van; Hackeng, TM Tilman; Merkx, M Maarten; Meijer, EW Bert
Source: ISSN:0947-6539.
Publication Year: 2009
Collection: Eindhoven University of Technology (TU/e): Research Portal
Description: The covalent synthesis of complex biomolecular systems such as multivalent protein dendrimers often proceeds with low efficiency, thereby making alternative strategies based on noncovalent chemistry of high interest. Here, the synthesis of protein dendrimers using a strong but noncovalent interaction between a peptide and complementary protein is proposed as an efficient strategy to arrive at dendrimers fully functionalized with protein domains. The association of S-peptide to S-protein results in the formation of an active enzyme (ribonuclease S) and therefore serves as an ideal system to explore this synthetic approach. Native chemical ligation was used to couple four S-peptides by means of their Cterminal thioester to a cysteine-functionalized dendritic scaffold, thus yielding a tetravalent S-peptide wedge. A fully functional ribonuclease S tetramer was prepared by addition of four equivalents of S-protein. Biophysical techniques (isothermal titration calorimetry (ITC), surface plasmon resonance (SPR), and mass spectrometry) and an enzymatic activity assay were used to verify the formation of the multivalent complex. The noncovalent synthetic strategy presented here provides access to well-defined, dynamic, semisynthetic protein assemblies in high yield and is therefore of interest to the field of nanomedicine as well as biomaterials. © 2009 Wiley-VCH Verlag GmbH & Cu. KGaA.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: http://repository.tue.nl/653778
Availability: http://repository.tue.nl/653778
Rights: Copyright (c) Lempens, EHM Edith ; Copyright (c) Baal, I Ingrid van ; Copyright (c) Dongen, JLJ Joost van ; Copyright (c) Hackeng, TM Tilman ; Copyright (c) Merkx, M Maarten ; Copyright (c) Meijer, EW Bert
Accession Number: edsbas.2575E70F
Database: BASE