Combinatorial synthesis, selection, and properties of esterase peptide dendrimers

Clouet, Anthony; Darbre, Tamis; Reymond, Jean‐Louis

doi:10.1002/bip.20394

Cited by 37 publications

(20 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This hypothesis is supported by findings that peptide dendrimers rich in histidine, and even nonpeptide polymers containing imidazole moities, can function as esterases. 46,47 The frequent occurrence of heme binding, peroxidase activity, and hydrolase activity in other systems based on the polypeptide backbone and natural amino acid side chains is consistent with our results with binary patterned de novo proteins, and suggests that rudimentary activity is relatively common in the feedstock of evolution.…”

Section: Functional Proteins Occur Frequently In Unselected Librariessupporting

confidence: 89%

Cofactor binding and enzymatic activity in an unevolved superfamily of de novo designed 4‐helix bundle proteins

et al. 2009

View full text Add to dashboard Cite

To probe the potential for enzymatic activity in unevolved amino acid sequence space, we created a combinatorial library of de novo 4-helix bundle proteins. This collection of novel proteins can be considered an ''artificial superfamily'' of helical bundles. The superfamily of 102-residue proteins was designed using binary patterning of polar and nonpolar residues, and expressed in Escherichia coli from a library of synthetic genes. Sequences from the library were screened for a range of biological functions including heme binding and peroxidase, esterase, and lipase activities. Proteins exhibiting these functions were purified and characterized biochemically. The majority of de novo proteins from this superfamily bound the heme cofactor, and a sizable fraction of the proteins showed activity significantly above background for at least one of the tested enzymatic activities. Moreover, several of the designed 4-helix bundles proteins showed activity in all of the assays, thereby demonstrating the functional promiscuity of unevolved proteins. These studies reveal that de novo proteins-which have neither been designed for function, nor subjected to evolutionary pressure (either in vivo or in vitro)-can provide rudimentary activities and serve as a ''feedstock'' for evolution.

show abstract

Section: Functional Proteins Occur Frequently In Unselected Librariessupporting

confidence: 89%

Cofactor binding and enzymatic activity in an unevolved superfamily of de novo designed 4‐helix bundle proteins

et al. 2009

View full text Add to dashboard Cite

show abstract

“…In order to overcome these drawbacks, the group initiated studies where the so-called split-and-mix technique was used to construct combinatorial libraries with as many as 65 536 different dendrimers. 64 The catalytic screening studies were carried out on this library, and the active candidates were separated from the rest, analyzed and finally resynthesized. By this technique the group found different dendritic aldolases, 65 and other types of esterases.…”

Section: Organocatalysis Near the Surfacementioning

confidence: 99%

Organocatalytic dendrimers

Rasmussen

Christensen

2012

Org. Biomol. Chem.

View full text Add to dashboard Cite

Dendrimers are a class of synthetic macromolecules that bridge the gap between polymers and small molecules. The dendritic structure provides both the possibility for compartmentalization of reagents as well as offering a multivalent surface, and they are in that respect similar to globular proteins. This perspective article reviews the growing field of organocatalysis with dendrimers and highlights the possibilities that are unattainable for small molecule catalysts.

show abstract

“…The injection volume was 100 μL, and detection of eluted samples was performed at 214 nm. These parameters were chosen based on optimization of previous reported HPLC methods of dendrimers [28,[40][41][42].…”

Section: High-performance Liquid Chromatographymentioning

confidence: 99%

Improved Methodology for Monitoring Poly(amidoamine) Dendrimers Surface Transformations and Product Quality by Ultra Performance Liquid Chromatography

Cason

Oehrle

Fabré

et al. 2008

Journal of Nanomaterials

View full text Add to dashboard Cite

Ultra performance liquid chromatography (UPLC) analysis was utilized for the first time as a methodology for monitoring poly(amidoamine) (PAMAM) dendrimer surface transformations and product quality. Results were compared to high-performance liquid chromatography (HPLC) and were found to provide a vastly improved analytical method for the characterization of dendrimer polydispersity and variance in a typical surface modification. The application of UPLC increased the average number of theoretical plates by a factor of 7 and reduced retention times of analytes by 36%, while improving the resolution capability to discriminate surface variances in dendrimers. The new UPLC procedures were used to monitor surface modification of [core: ethylenediamine]; (G = 4);dendri-poly(amidoamine)-(NH2)64(i.e., [EDA]; (G4);dendri-PAMAM-(NH2)64) to produce biotinylated dendrimer conjugates. The enhanced sensitivity and efficiency of the UPLC analyses allowed resolution of biotin substituent levels and a better characterization of the targeted dendrimer conjugates compared to traditional HPLC methodology.

show abstract

Combinatorial synthesis, selection, and properties of esterase peptide dendrimers

Cited by 37 publications

References 36 publications

Cofactor binding and enzymatic activity in an unevolved superfamily of de novo designed 4‐helix bundle proteins

Cofactor binding and enzymatic activity in an unevolved superfamily of de novo designed 4‐helix bundle proteins

Organocatalytic dendrimers

Improved Methodology for Monitoring Poly(amidoamine) Dendrimers Surface Transformations and Product Quality by Ultra Performance Liquid Chromatography

Contact Info

Product

Resources

About