Proteomimetic surface fragments distinguish targets by function

Tököli, Attila; Mag, Beáta; Bartus, Éva; Wéber, Edit; Szakonyi, Gerda; Simon, Márton A; Czibula, Ágnes; Monostori, Éva; Nyitray, László; Martinek, Tamás A.

doi:10.1039/d0sc03525d

Cited by 9 publications

(20 citation statements)

References 96 publications

(97 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…K d ranges are color coded as shown on the right. The vertical axis and horizontal axis represents the β-amino acid in the second and fifth positions, respectively [11]. Some S100 members favored multiple fragments (e.g.…”

Section: Resultsmentioning

confidence: 99%

“…small patches of the binding interface) displaying reduced structural complexity [8–10]. Local surface mimetic (LSM) foldamers having water-stable H14 helical conformation proved to be efficient probes for screening these shallow binding clefts of different protein targets [11]. In a high-throughput (HTP) experimental setup, the binding properties of the S100ome can be characterized comprehensively by using this LSM foldamer library.…”

Section: Introductionmentioning

confidence: 99%

“…( Fig 1A ). The bulky cyclic amino acids in the helix (trans-2-aminocyclohexancarboxylic acid) shield the proteinogenic side chains introduced by β 3 -amino acid derivatives from the solvents [11].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Binding Profile Mapping of the S100 Protein Family Using a High-throughput Local Surface Mimetic Holdup Assay

Simon

Bartus

Mag

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

S100 proteins are small, typically homodimeric, vertebrate-specific EF-hand proteins that establish Ca2+-dependent protein-protein interactions in the intra- and extracellular environment and are overexpressed in various pathologies. There are about 20 distinct human S100 proteins with numerous potential partner proteins. Here, we used a quantitative holdup assay to measure affinity profiles of most members of the S100 protein family against a library of chemically synthetized foldamers. The profiles allowed us to quantitatively map the binding promiscuity of each member towards the foldamer library. Since the library was designed to systematically contain most binary natural amino acid side chain combinations, the data also provide insight into the promiscuity of each S100 protein towards all potential naturally-occurring S100 partners in the human proteome. Such information will be precious for future drug design of modulators of S100 pathological activities.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Binding Profile Mapping of the S100 Protein Family Using a High-throughput Local Surface Mimetic Holdup Assay

Simon

Bartus

Mag

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Mapping the binding surface of proteins can be performed with short recognition elements (i.e., small patches of the binding interface) displaying reduced structural complexity [9][10][11] . Local surface mimetic (LSM) foldamers having water-stable H14 helical conformation proved to be e cient probes for screening these shallow binding clefts of different protein targets 12 . In a high-throughput (HTP) experimental setup, the binding properties of the S100ome can be characterized comprehensively by using this LSM foldamer library.…”

Section: Introductionmentioning

confidence: 99%

“…1A). The bulky cyclic amino acids in the helix (trans-2-aminocyclohexancarboxylic acid) shield the proteinogenic side chains introduced by β 3 -amino acid derivatives from the solvent molecules 12 .…”

Section: Introductionmentioning

confidence: 99%

Promiscuity Mapping of the S100 Protein Family Using a High-Throughput Local Surface Mimetic Holdup Assay

Simon

Bartus

Mag

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

S100 proteins are small, typically homodimeric, vertebrate-specific EF-hand proteins that establish Ca2+-dependent protein-protein interactions in the intra- and extracellular environment and are overexpressed in various pathologies. There are about 20 distinct human S100 proteins with numerous potential partner proteins. Here, we used a quantitative holdup assay to measure affinity profiles of most members of the S100 protein family against a library of chemically synthetized foldamers. The profiles allowed us to quantitatively map the binding promiscuity of each member towards the foldamer library. Since the library was designed to systematically contain most binary natural amino acid side chain combinations, the data also provide insight into the promiscuity of each S100 protein towards all potential naturally occurring S100 partners in the human proteome. Such information will be precious for future drug design to interfere with S100 related pathologies.

show abstract

Harnessing Aromatic‐Histidine Interactions through Synergistic Backbone Extension and Side Chain Modification

Yu,

Kreitler,

Chiu

et al. 2023

Angewandte Chemie

View full text Add to dashboard Cite

Peptide engineering efforts have delivered drugs for diverse human diseases. Side chain alteration is among the most common approaches to designing new peptides for specific applications. The peptide backbone can be modified as well, but this strategy has received relatively little attention. Here we show that new and favorable contacts between a His side chain on a target protein and an aromatic side chain on a synthetic peptide ligand can be engineered by rational and coordinated side chain modification and backbone extension. Side chain modification alone was unsuccessful. Binding measurements, high‐resolution structural studies and pharmacological outcomes all support the synergy between backbone and side chain modification in engineered ligands of the parathyroid hormone receptor‐1, which is targeted by osteoporosis drugs. These results should motivate other structure‐based designs featuring coordinated side chain modification and backbone extension to enhance the engagement of peptide ligands with target proteins.

show abstract

Proteomimetic surface fragments distinguish targets by function

Abstract: The fragment-centric design promises a means to develop complex xenobiotic protein surface mimetics, but it is challenging to find locally biomimetic structures. To address this issue, foldameric local surface mimetic...

Cited by 9 publications

References 96 publications

Binding Profile Mapping of the S100 Protein Family Using a High-throughput Local Surface Mimetic Holdup Assay

Binding Profile Mapping of the S100 Protein Family Using a High-throughput Local Surface Mimetic Holdup Assay

Promiscuity Mapping of the S100 Protein Family Using a High-Throughput Local Surface Mimetic Holdup Assay

Harnessing Aromatic‐Histidine Interactions through Synergistic Backbone Extension and Side Chain Modification

Contact Info

Product

Resources

About