Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis of Fmoc-Triazine Amino Acids and Its Application in the Synthesis of Short Antibacterial Peptidomimetics.

ABSTRACT: To combat the escalating rise of antibacterial resistance, the development of antimicrobial peptides (AMPs) with a unique mode of action is considered an attractive strategy. However, proteolytic degradation of AMPs remains the greatest challenge in their transformation into therapeutics. Herein, we synthesized Fmoc-triazine amino acids that differ from each other by anchoring either cationic or hydrophobic residues. These unnatural amino acids were adopted for solid-phase peptide synthesis (SPPS) to synthesize a series of amphipathic antimicrobial peptidomimetics. From the antimicrobial screening, we found that the trimer, BJK-4 is the most potent short antimicrobial peptidomimetic without showing hemolytic activity and it displayed enhanced proteolytic stability. Moreover, the mechanism of action to kill bacteria was found to be an intracellular targeting.

SUBMITTER: Gunasekaran P

PROVIDER: S-EPMC7279249 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis of Fmoc-Triazine Amino Acids and Its Application in the Synthesis of Short Antibacterial Peptidomimetics.

Gunasekaran Pethaiah P Kim Eun Young EY Lee Jian J Ryu Eun Kyoung EK Shin Song Yub SY Bang Jeong Kyu JK

International journal of molecular sciences 20200520 10

To combat the escalating rise of antibacterial resistance, the development of antimicrobial peptides (AMPs) with a unique mode of action is considered an attractive strategy. However, proteolytic degradation of AMPs remains the greatest challenge in their transformation into therapeutics. Herein, we synthesized Fmoc-triazine amino acids that differ from each other by anchoring either cationic or hydrophobic residues. These unnatural amino acids were adopted for solid-phase peptide synthesis (SPP ...[more]

PMID: 32443730

Similar Datasets

One-Step Synthesis of 3-(Fmoc-amino acid)-3,4-diaminobenzoic Acids.

Project description:A one-step method for synthesizing 3-(Fmoc-amino acid)-3,4-diaminobenzoic acids was used to prepare preloaded diaminobenzoate resin. The coupling of free diaminobenzoic acid and Fmoc-amino acids gave pure products in 40-94% yield without any purification step in addition to precipitation except for histidine. For the proline residue, crude products were collected and used for solid-phase peptide synthesis to give a moderate yield of a pentapeptide. In addition, this method was used to prepare unusual amino acid derivatives, namely, (2-naphthyl) alanine and 6-aminohexanoic acid derivatives, in 50 and 65% yield, respectively.

| S-EPMC10634083 | biostudies-literature

Synthesis of HDAC Substrate Peptidomimetic Inhibitors Using Fmoc Amino Acids Incorporating Zinc-Binding Groups.

Project description:Syntheses of Fmoc amino acids having zinc-binding groups were prepared and incorporated into substrate inhibitor H3K27 peptides using Fmoc/tBu solid-phase peptide synthesis (SPPS). Peptide 11, prepared using Fmoc-Asu(NHOtBu)-OH, is a potent inhibitor (IC50 = 390 nM) of the core NuRD corepressor complex (HDAC1-MTA1-RBBP4). The Fmoc amino acids have the potential to facilitate the rapid preparation of substrate peptidomimetic inhibitor (SPI) libraries in the search for selective HDAC inhibitors.

| S-EPMC6503537 | biostudies-literature

With unprotected amino acids to tetrazolo peptidomimetics.

Project description:Here we describe the direct usage of C,N-unprotected amino acids in Ugi-tetrazole reactions to produce a novel class of acid-tetrazole compounds. Surprisingly, only the tetrazole Ugi product is found and not traces of other possible Ugi type reactions. Based on this reaction pathway we have designed the synthesis of novel tetrazole-peptidomimetics. A high level of structural diversity can be achieved using this isocyanide based multicomponent reaction (IMCR), providing a platform for the production of functionalized building blocks for novel bioactive molecules and nontraditional scaffolds which previously were not accessible.

| S-EPMC5588861 | biostudies-literature

Caged O-phosphorothioyl amino acids as building blocks for Fmoc-based solid phase peptide synthesis.

Project description:The synthesis of 1-(2-nitrophenylethyl) caged O-phosphorothioylserine, -threonine and -tyrosine derivatives is reported. These amino acid building blocks can be directly incorporated into peptides by Fmoc-based solid phase synthesis as their pentafluorophenyl esters or as symmetric anhydrides. Upon irradiation with UV light, the thiophosphate group, representing a hydrolysis resistant phosphate analog, is revealed.

| S-EPMC2699315 | biostudies-literature

Evaluating Fmoc-amino acids as selective inhibitors of butyrylcholinesterase.

Project description:Cholinesterases are involved in neuronal signal transduction, and perturbation of function has been implicated in diseases, such as Alzheimer's and Huntington's disease. For the two major classes of cholinesterases, such as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), previous studies reported BChE activity is elevated in patients with Alzheimer's disease, while AChE levels remain the same or decrease. Thus, the development of potent and specific inhibitors of BChE have received much attention as a potential therapeutic in the alleviation of neurodegenerative diseases. In this study, we evaluated amino acid analogs as selective inhibitors of BChE. Amino acid analogs bearing a 9-fluorenylmethyloxycarbonyl (Fmoc) group were tested, as the Fmoc group has structural resemblance to previously described inhibitors. We identified leucine, lysine, and tryptophan analogs bearing the Fmoc group as selective inhibitors of BChE. The Fmoc group contributed to inhibition, as analogs bearing a carboxybenzyl group showed ~tenfold higher values for the inhibition constant (K I value). Inclusion of a t-butoxycarbonyl on the side chain of Fmoc tryptophan led to an eightfold lower K I value compared to Fmoc tryptophan alone suggesting that modifications of the amino acid side chains may be designed to create inhibitors with higher affinity. Our results identify Fmoc-amino acids as a scaffold upon which to design BChE-specific inhibitors and provide the foundation for further experimental and computational studies to dissect the interactions that contribute to inhibitor binding.

| S-EPMC5802362 | biostudies-literature

Correction to "Development of Fmoc-Protected Bis-Amino Acids toward Automated Synthesis of Highly Functionalized Spiroligomers".

Project description: Not available

| S-EPMC9942684 | biostudies-literature

Project description:The chemical similarity of antibacterial cyclic peptides and peptidomimetics was studied in order to identify new promising cyclic scaffolds. A large descriptor space coupled with cluster analysis was employed to digitize known antibacterial structures and to gauge the potential of new peptidomimetic macrocycles, which were conveniently synthesized by acylbenzotriazole methodology. Some of the synthesized compounds were tested against an array of microorganisms and showed antibacterial activity against Bordetella bronchistepica, Micrococcus luteus, and Salmonella typhimurium.

| S-EPMC3458733 | biostudies-literature

Optimized syntheses of Fmoc azido amino acids for the preparation of azidopeptides.

Project description:The rise of CuI-catalyzed click chemistry has initiated an increased demand for azido and alkyne derivatives of amino acid as precursors for the synthesis of clicked peptides. However, the use of azido and alkyne amino acids in peptide chemistry is complicated by their high cost. For this reason, we investigated the possibility of the in-house preparation of a set of five Fmoc azido amino acids: ?-azido l-alanine and d-alanine, ?-azido l-homoalanine, ?-azido l-ornithine and ?-azido l-lysine. We investigated several reaction pathways described in the literature, suggested several improvements and proposed several alternative routes for the synthesis of these compounds in high purity. Here, we demonstrate that multigram quantities of these Fmoc azido amino acids can be prepared within a week or two and at user-friendly costs. We also incorporated these azido amino acids into several model tripeptides, and we observed the formation of a new elimination product of the azido moiety upon conditions of prolonged couplings with 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate/DIPEA. We hope that our detailed synthetic protocols will inspire some peptide chemists to prepare these Fmoc azido acids in their laboratories and will assist them in avoiding the too extensive costs of azidopeptide syntheses. Experimental procedures and/or analytical data for compounds 3-5, 20, 25, 26, 30 and 43-47 are provided in the supporting information. © 2017 The Authors Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.

| S-EPMC5347871 | biostudies-other

An index for characterization of natural and non-natural amino acids for peptidomimetics.

Project description:Bioactive peptides and peptidomimetics play a pivotal role in the regulation of many biological processes such as cellular apoptosis, host defense, and biomineralization. In this work, we develop a novel structural matrix, Index of Natural and Non-natural Amino Acids (NNAAIndex), to systematically characterize a total of 155 physiochemical properties of 22 natural and 593 non-natural amino acids, followed by clustering the structural matrix into 6 representative property patterns including geometric characteristics, H-bond, connectivity, accessible surface area, integy moments index, and volume and shape. As a proof-of-principle, the NNAAIndex, combined with partial least squares regression or linear discriminant analysis, is used to develop different QSAR models for the design of new peptidomimetics using three different peptide datasets, i.e., 48 bitter-tasting dipeptides, 58 angiotensin-converting enzyme inhibitors, and 20 inorganic-binding peptides. A comparative analysis with other QSAR techniques demonstrates that the NNAAIndex method offers a stable and predictive modeling technique for in silico large-scale design of natural and non-natural peptides with desirable bioactivities for a wide range of applications.

| S-EPMC3720802 | biostudies-literature

Non-Canonical Amino Acids as Building Blocks for Peptidomimetics: Structure, Function, and Applications.

Project description:This review provides a fresh overview of non-canonical amino acids and their applications in the design of peptidomimetics. Non-canonical amino acids appear widely distributed in nature and are known to enhance the stability of specific secondary structures and/or biological function. Contrary to the ubiquitous DNA-encoded amino acids, the structure and function of these residues are not fully understood. Here, results from experimental and molecular modelling approaches are gathered to classify several classes of non-canonical amino acids according to their ability to induce specific secondary structures yielding different biological functions and improved stability. Regarding side-chain modifications, symmetrical and asymmetrical α,α-dialkyl glycines, Cα to Cα cyclized amino acids, proline analogues, β-substituted amino acids, and α,β-dehydro amino acids are some of the non-canonical representatives addressed. Backbone modifications were also examined, especially those that result in retro-inverso peptidomimetics and depsipeptides. All this knowledge has an important application in the field of peptidomimetics, which is in continuous progress and promises to deliver new biologically active molecules and new materials in the near future.

| S-EPMC10296201 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data