Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Construction of diverse peptide structural architectures via chemoselective peptide ligation.

ABSTRACT: Herein, we report the development of a facile synthetic strategy for constructing diverse peptide structural architectures via chemoselective peptide ligation. The key advancement involved is to utilize the benzofuran moiety as the peptide salicylaldehyde ester surrogate, and Dap-Ser/Lys-Ser dipeptide as the hydroxyl amino functionality, which could be successfully introduced at the side chain of peptides enabling peptide ligation. With this method, the side chain-to-side chain cyclic peptide, branched/bridged peptides, tailed cyclic peptides and multi-cyclic peptides have been designed and successfully synthesized with native peptidic linkages at the ligation sites. This strategy has provided an alternative strategic opportunity for synthetic peptide development. It also serves as an inspiration for the structural design of PPI inhibitors with new modalities.

SUBMITTER: Cheung CHP

PROVIDER: S-EPMC8153220 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Chemoselective cross-linking and functionalization of alginate via Staudinger ligation.

Project description:In this study, we demonstrate the applicability of functionalized alginate to serve as a platform for the covalent cross-linking or immobilization of complementary phosphine functionalized groups via the chemoselective Staudinger ligation scheme. Azide groups were covalently linked to alginate through a heterobifunctional polyethylene glycol (PEG) linker and carbodiimide. Degree of azide functionalization was varied as a function of carbodiimide concentration and determined by proton nuclear magnetic resonance ((1)H NMR) and infrared spectroscopy. Spontaneous and covalently cross-linked alginate-PEG gels were generated via the Staudinger ligation scheme upon incubation of the azide functionalized alginate with PEG chains having 1-methyl-2-diphenylphosphino-terephthalate (MDT) as end groups. Modulation of the MDT to N(3) ratio resulted in variability of gel characteristics. In addition, azide functionalized alginate retained its capacity to instantaneously form hydrogels via electrostatic interaction with multivalent cations such as Ca(2+) and Ba(2+). Subsequently, covalent linkage of phosphine functionalized agents postgelation of the alginate was feasible, as illustrated via linkage of MDT-PEG-carboxyfluorescein. Capitalization of the chemoselective and cell compatible Staudinger ligation scheme for covalent cross-linking of alginate hydrogels may enhance the utility of this polymer for the stable encapsulation of various cell types, in addition to their use in the immobilization of labeling agents, proteins, and other bioactive molecules.

| S-EPMC2996242 | biostudies-literature

Glycoconjugate synthesis using chemoselective ligation.

Project description:Chemoselective ligation of carbohydrates and polypeptides was achieved using an adipic acid dihydrazide cross-linker. The reducing end of a carbohydrate is efficiently attached to peptides in two steps, constructing a glycoconjugate in high yield and with high regioselectivity, enabling the production of homogeneous glycoconjugates.

| S-EPMC6431789 | biostudies-literature

Prebiotically plausible oligoribonucleotide ligation facilitated by chemoselective acetylation.

Project description:The recent synthesis of pyrimidine ribonucleoside-2',3'-cyclic phosphates under prebiotically plausible conditions has strengthened the case for the involvement of ribonucleic acid (RNA) at an early stage in the origin of life. However, a prebiotic conversion of these weakly activated monomers, and their purine counterparts, to the 3',5'-linked RNA polymers of extant biochemistry has been lacking (previous attempts led only to short oligomers with mixed linkages). Here we show that the 2'-hydroxyl group of oligoribonucleotide-3'-phosphates can be chemoselectively acetylated in water under prebiotically credible conditions, which allows rapid and efficient template-directed ligation. The 2'-O-acetyl group at the ligation junction of the product RNA strand can be removed under conditions that leave the internucleotide bonds intact. Remarkably, acetylation of mixed oligomers that possess either 2'- or 3'-terminal phosphates is selective for the 2'-hydroxyl group of the latter. This newly discovered chemistry thus suggests a prebiotic route from ribonucleoside-2',3'-cyclic phosphates to predominantly 3',5'-linked RNA via partially 2'-O-acetylated RNA.

| S-EPMC4074891 | biostudies-literature

Spontaneous formation of structurally diverse membrane channel architectures from a single antimicrobial peptide.

Project description:Many antimicrobial peptides (AMPs) selectively target and form pores in microbial membranes. However, the mechanisms of membrane targeting, pore formation and function remain elusive. Here we report an experimentally guided unbiased simulation methodology that yields the mechanism of spontaneous pore assembly for the AMP maculatin at atomic resolution. Rather than a single pore, maculatin forms an ensemble of structurally diverse temporarily functional low-oligomeric pores, which mimic integral membrane protein channels in structure. These pores continuously form and dissociate in the membrane. Membrane permeabilization is dominated by hexa-, hepta- and octamers, which conduct water, ions and small dyes. Pores form by consecutive addition of individual helices to a transmembrane helix or helix bundle, in contrast to current poration models. The diversity of the pore architectures-formed by a single sequence-may be a key feature in preventing bacterial resistance and could explain why sequence-function relationships in AMPs remain elusive.

| S-EPMC5121426 | biostudies-literature

Chemoselective ligation in the functionalization of polysaccharide-based particles.

Project description:Despite the promise of precisely targeted or otherwise functionalized polymeric particulate drug delivery vehicles, typical biocompatible particles are generally not amenable to facile and selective surface modification. Herein, we report the development of a simple, mild, and chemoselective strategy for the conjugation of biologically active molecules to the surface of dextran-based microparticles. Alkoxyamine-bearing reagents were used to form stable oxime conjugates with latent aldehyde functionality present in reducing carbohydrate chain ends. We demonstrate the functionalization of dextran-based microparticles with a fluorophore as well as a cell-penetrating peptide sequence, which facilitated the delivery of cargo to nonphagocytic cells leading to a 60-fold increase in the expression of a reporter gene when plasmid DNA-loaded particles were used.

| S-EPMC2759380 | biostudies-literature

General chemoselective and redox-responsive ligation and release strategy.

Project description:We report a switchable redox click and cleave reaction strategy for conjugating and releasing a range of molecules on demand. This chemoselective redox-responsive ligation (CRRL) and release strategy is based on a redox switchable oxime linkage that is controlled by mild chemical or electrochemical redox signals and can be performed at physiological conditions without the use of a catalyst. Both conjugation and release reactions are kinetically well behaved and quantitative. The CRRL strategy is synthetically modular and easily monitored and characterized by routine analytical techniques. We demonstrate how the CRRL strategy can be used for the dynamic generation of cyclic peptides and the ligation of two different peptides that are stable but can be selectively cleaved upon changes in the redox environment. We also demonstrate a new redox based delivery of cargoes to live cells strategy via the CRRL methodology by synthesizing a FRET redox-responsive probe that is selectively activated within a cellular environment. We believe the ease of the CRRL strategy should find wide use in a range of applications in biology, tissue engineering, nanoscience, synthetic chemistry, and material science and will expand the suite of current conjugation and release strategies.

| S-EPMC3983135 | biostudies-literature

Chemoselective ligation of sulfinic acids with aryl-nitroso compounds.

Project description:Making a comeback: The inefficient condensation of sulfinic acid and aryl nitroso compounds has been transformed into a chemoselective process that converts sulfinic acid into stable cyclic sulfonamide analogues (see scheme). This ligation proceeds rapidly under aqueous conditions in high yield, and lays the groundwork for the development of sulfinic acid detection methods in biological systems.

| S-EPMC3523331 | biostudies-literature

Self-Assembly of Antiferromagnetically-Coupled Copper(II) Supramolecular Architectures with Diverse Structural Complexities.

Project description:The self-assembly of 2,6-diformyl-4-methylphenol (DFMP) and 1-amino-2-propanol (AP)/2-amino-1,3-propanediol (APD) in the presence of copper(II) ions results in the formation of six new supramolecular architectures containing two versatile double Schiff base ligands (H3L and H5L1) with one-, two-, or three-dimensional structures involving diverse nuclearities: tetranuclear [Cu4(HL2-)2(N3)4]·4CH3OH·56H2O (1) and [Cu4(L3-)2(OH)2(H2O)2] (2), dinuclear [Cu2(H3L12-)(N3)(H2O)(NO3)] (3), polynuclear {[Cu2(H3L12-)(H2O)(BF4)(N3)]·H2O}n (4), heptanuclear [Cu7(H3L12-)2(O)2(C6H5CO2)6]·6CH3OH·44H2O (5), and decanuclear [Cu10(H3L12-)4(O)2(OH)2(C6H5CO2)4] (C6H5CO2)2·20H2O (6). X-ray studies have revealed that the basic building block in 1, 3, and 4 is comprised of two copper centers bridged through one μ-phenolate oxygen atom from HL2- or H3L12-, and one μ-1,1-azido (N3-) ion and in 2, 5, and 6 by μ-phenoxide oxygen of L3- or H3L12- and μ-O2- or μ3-O2- ions. H-bonding involving coordinated/uncoordinated hydroxy groups of the ligands generates fascinating supramolecular architectures with 1D-single chains (1 and 6), 2D-sheets (3), and 3D-structures (4). In 5, benzoate ions display four different coordination modes, which, in our opinion, is unprecedented and constitutes a new discovery. In 1, 3, and 5, Cu(II) ions in [Cu2] units are antiferromagnetically coupled, with J ranging from -177 to -278 cm-1.

| S-EPMC7734591 | biostudies-literature

Segregated Protein-Cucurbit[7]uril Crystalline Architectures via Modulatory Peptide Tectons.

Project description:One approach to protein assembly involves water-soluble supramolecular receptors that act like glues. Bionanoarchitectures directed by these scaffolds are often system-specific, with few studies investigating their customization. Herein, the modulation of cucurbituril-mediated protein assemblies through the inclusion of peptide tectons is described. Three peptides of varying length and structural order were N-terminally appended to RSL, a β-propeller building block. Each fusion protein was incorporated into crystalline architectures mediated by cucurbit[7]uril (Q7). A trimeric coiled-coil served as a spacer within a Q7-directed sheet assembly of RSL, giving rise to a layered material of varying porosity. Within the spacer layers, the coiled-coils were dynamic. This result prompted consideration of intrinsically disordered peptides (IDPs) as modulatory tectons. Similar to the coiled-coil, a mussel adhesion peptide (Mefp) also acted as a spacer between protein-Q7 sheets. In contrast, the fusion of a nucleoporin peptide (Nup) to RSL did not recapitulate the sheet assembly. Instead, a Q7-directed cage was adopted, within which disordered Nup peptides were partially "captured" by Q7 receptors. IDP capture occurred by macrocycle recognition of an intrapeptide Phe-Gly motif in which the benzyl group was encapsulated by Q7. The modularity of these protein-cucurbituril architectures adds a new dimension to macrocycle-mediated protein assembly. Segregated protein crystals, with alternating layers of high and low porosity, could provide a basis for new types of materials.

| S-EPMC8596587 | biostudies-literature

Enabling Peptide Ligation at Aromatic Junction Mimics via Native Chemical Ligation and Palladium-Mediated S-Arylation.

Project description:Synthetic strategies to assemble peptide fragments are in high demand to access homogeneous proteins for various applications. Here, we combined native chemical ligation (NCL) and Pd-mediated Cys arylation to enable practical peptide ligation at aromatic junctions. The utility of one-pot NCL and S-arylation at the Phe and Tyr junctions was demonstrated and employed for the rapid chemical synthesis of the DNA-binding domains of the transcription factors Myc and Max. Organometallic palladium reagents coupled with NCL enabled a practical strategy to assemble peptides at aromatic junctions.

| S-EPMC10324392 | 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