Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

?-Turn Mimics by Chemical Ligation.

ABSTRACT: We report a simple reductive amination protocol to ligate two peptides, while simultaneously installing a ?-turn mimic at the ligation junction. This strategy uses commercially available materials, mild chemical conditions, and a chemoselective ligation reaction of unprotected peptide substrates accessed through standard solid phase methods. This system was implemented in a designed ?-hairpin system, and biophysical analysis demonstrates effective mimicry of the ?-turn.

SUBMITTER: Crecente-Garcia S

PROVIDER: S-EPMC7304061 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

β-Turn Mimics by Chemical Ligation.

Crecente-Garcia Selma S Neckebroeck Albane A Clark J Stephen JS Smith Brian O BO Thomson Andrew R AR

Organic letters 20200514 11

We report a simple reductive amination protocol to ligate two peptides, while simultaneously installing a β-turn mimic at the ligation junction. This strategy uses commercially available materials, mild chemical conditions, and a chemoselective ligation reaction of unprotected peptide substrates accessed through standard solid phase methods. This system was implemented in a designed β-hairpin system, and biophysical analysis demonstrates effective mimicry of the β-turn. ...[more]

PMID: 32406695

Similar Datasets

Pyrrole-based scaffolds for turn mimics.

Project description:Two amino acid derived synthons were combined to give homopropargylic amines 2. Platinum dichloride was used to cyclize these intermediates into pyrroles 3 which collapsed to the target secondary structure mimics 1 on treatment with base. Side chains of these compounds overlay with an idealized type 1 β-turn and with an inverse γ-turn.

| S-EPMC3077957 | biostudies-literature

Evaluating beta-turn mimics as beta-sheet folding nucleators.

Project description:Beta-turns are common conformations that enable proteins to adopt globular structures, and their formation is often rate limiting for folding. Beta-turn mimics, molecules that replace the i + 1 and i + 2 amino acid residues of a beta-turn, are envisioned to act as folding nucleators by preorganizing the pendant polypeptide chains, thereby lowering the activation barrier for beta-sheet formation. However, the crucial kinetic experiments to demonstrate that beta-turn mimics can act as strong nucleators in the context of a cooperatively folding protein have not been reported. We have incorporated 6 beta-turn mimics simulating varied beta-turn types in place of 2 residues in an engineered beta-turn 1 or beta-bulge turn 1 of the Pin 1 WW domain, a three-stranded beta-sheet protein. We present 2 lines of kinetic evidence that the inclusion of beta-turn mimics alters beta-sheet folding rates, enabling us to classify beta-turn mimics into 3 categories: those that are weak nucleators but permit Pin WW folding, native-like nucleators, and strong nucleators. Strong nucleators accelerate folding relative to WW domains incorporating all alpha-amino acid sequences. A solution NMR structure reveals that the native Pin WW beta-sheet structure is retained upon incorporating a strong E-olefin nucleator. These beta-turn mimics can now be used to interrogate protein folding transition state structures and the 2 kinetic analyses presented can be used to assess the nucleation capacity of other beta-turn mimics.

| S-EPMC2708776 | biostudies-literature

Cyclopenta[<i>d</i>]isoxazoline β-Turn Mimics: Synthetic Approach, Turn Driving Force, Scope, and Limitations.

Project description:Model β-turn inducers were prepared from constrained oxazanorbornene aminols. Taking advantage of the starting materials geometry, new diastereoisomeric compounds were synthesized, introducing different amino acidic residues. The products were spectroscopically characterized (VT and NMR titration). Temperature coefficients in dimethyl sulfoxide denote the existence of an intramolecular hydrogen bond. Chiroptical properties disclosed a β-turn arrangement of the synthesized compounds. The fused isoxazoline ring constraints the cyclopentane moiety, stabilizing a boatlike conformation that ensures the turn efficiency but limiting the accessibility to hindered amino acids.

| S-EPMC6645019 | biostudies-literature

Hydrogels cross-linked by native chemical ligation.

Project description:We describe the use of native chemical ligation (NCL) reaction to covalently cross-link soluble polymers into hydrogels. Macromonomers consisting of a four-armed poly(ethylene glycol) (PEG) core end-functionalized with either thioester or N-terminal cysteine peptide were designed and synthesized. Upon mixing aqueous solutions of the thioester and N-terminal cysteine macromonomers, rigid hydrogels formed within minutes. The gelation time was affected by choice of buffer, pH, polymer concentration, reaction temperature, and chemical composition of the N-terminal cysteine conjugate. The kinetics of gel formation and the viscoelastic behavior of selected hydrogels were further studied by oscillatory rheology, which demonstrated a minimum gel formation time of approximately two minutes and the formation of an elastic cross-linked hydrogel via the NCL reaction. A useful feature of this hydrogel strategy is the regeneration of thiol functional groups as a result of the NCL reaction, thereby allowing functionalization of the polymer hydrogel with biomolecules. This was demonstrated by conjugation of a maleimide-GRGDSPG-NH(2) peptide to an NCL hydrogel, permitting the attachment of human mesenchymal stem cells (hMSCs) on the hydrogel. Due to the mild reaction conditions, chemoselectivity, and potential for biological functionalization, our approach may prove useful as a general method for hydrogel formation, including hydrogels intended for biomedical applications.

| S-EPMC2790863 | biostudies-literature

Total chemical synthesis of human interferon alpha-2b via native chemical ligation.

Project description:Interferon-alpha (IFN?) is a cytokine that orchestrates innate and adaptive immune responses and potently inhibits proliferation of normal and tumor cells. These properties have warranted the use of IFN? in clinical practice for the treatment of several viral infections and malignancies. However, overexpression of IFN? leads to immunopathology observed in the context of chronic viral infections and autoimmune conditions. Thus, it is desirable to develop therapeutic approaches that aim at suppressing excessive IFN? production. To that end, artificial evolution of peptides from phage display libraries represents a strategy that seeks to disrupt the interaction between IFN? and its cell surface receptor and thus inhibit the ensuing biological effects. Mirror-image phage display that screens peptide libraries against the D-enantiomer is particularly attractive because it allows for identification of proteolysis-resistant D-peptide inhibitors. This approach, however, relies on the availability of chemically synthesized D-IFN? composed entirely of D-amino acids. Here, we describe the synthesis and biological properties of IFN?2b of 165 amino acid residues produced by native chemical ligation, which represents an important first step toward the discovery of D-peptide antagonists with potential therapeutic applications.

| S-EPMC4480187 | biostudies-literature

Protein chemical synthesis by serine and threonine ligation.

Project description:An efficient method has been developed for the salicylaldehyde ester-mediated ligation of unprotected peptides at serine (Ser) or threonine (Thr) residues. The utility of this peptide ligation approach has been demonstrated through the convergent syntheses of two therapeutic peptides--ovine-corticoliberin and Forteo--and the human erythrocyte acylphosphatase protein (?11 kDa). The requisite peptide salicylaldehyde ester precursor is prepared in an epimerization-free manner via Fmoc-solid-phase peptide synthesis.

| S-EPMC3637748 | biostudies-literature

In situ vesicle formation by native chemical ligation.

Project description:Phospholipid vesicles are of intense fundamental and practical interest, yet methods for their de novo generation from reactive precursors are limited. A non-enzymatic and chemoselective method to spontaneously generate phospholipid membranes from water-soluble starting materials would be a powerful tool for generating vesicles and studying lipid membranes. Here we describe the use of native chemical ligation (NCL) to rapidly prepare phospholipids spontaneously from thioesters. While NCL is one of the most popular tools for synthesizing proteins and nucleic acids, to our knowledge this is the first example of using NCL to generate phospholipids de novo. The lipids are capable of in situ synthesis and self-assembly into vesicles that can grow to several microns in diameter. The selectivity of the NCL reaction makes in situ membrane formation compatible with biological materials such as proteins. This work expands the application of NCL to the formation of phospholipid membranes.

| S-EPMC4418804 | biostudies-literature

Chemical ligation of oligonucleotides using an electrophilic phosphorothioester.

Project description:We developed a new approach for chemical ligation of oligonucleotides using the electrophilic phosphorothioester (EPT) group. A nucleophilic phosphorothioate group on oligonucleotides was converted into the EPT group by treatment with Sanger's reagent (1-fluoro-2,4-dinitrobenzene). EPT oligonucleotides can be isolated, stored frozen, and used for the ligation reaction. The reaction of the EPT oligonucleotide and an amino-modified oligonucleotide took place without any extra reagents at pH 7.0-8.0 at room temperature, and resulted in a ligation product with a phosphoramidate bond with a 39-85% yield. This method has potential uses in biotechnology and chemical biology.

| S-EPMC5499596 | biostudies-literature

Incorporating thioamides into proteins by native chemical ligation.

Project description:The thioamide is a versatile replacement of the peptide backbone with altered hydrogen bonding and conformational preferences, as well the ability participate in energy and electron transfer processes. Semi-synthetic incorporation of a thioamide into a protein can be used to study protein folding or protein/protein interactions using these properties. Semi-synthesis also provides the opportunity to study the role of thioamides in natural proteins. Here we outline the semi-synthesis of a model protein, the B1 domain of protein G (GB1) with a thioamide at the N-terminus or the C-terminus. The thioamide is synthetically incorporated into a fragment by solid-phase peptide synthesis, whereas the remainder of the protein is recombinantly expressed. Then, the two fragments are joined by native chemical ligation. The explicit protocol for GB1 synthesis is accompanied by examples of applications with GB1 and other proteins in structural biology and protein misfolding studies.

| S-EPMC8617429 | biostudies-literature

Rapid Bioorthogonal Chemistry Turn-on through Enzymatic or Long Wavelength Photocatalytic Activation of Tetrazine Ligation.

Project description:Rapid bioorthogonal reactivity can be induced by controllable, catalytic stimuli using air as the oxidant. Methylene blue (4 μM) irradiated with red light (660 nm) catalyzes the rapid oxidation of a dihydrotetrazine to a tetrazine thereby turning on reactivity toward trans-cyclooctene dienophiles. Alternately, the aerial oxidation of dihydrotetrazines can be efficiently catalyzed by nanomolar levels of horseradish peroxidase under peroxide-free conditions. Selection of dihydrotetrazine/tetrazine pairs of sufficient kinetic stability in aerobic aqueous solutions is key to the success of these approaches. In this work, polymer fibers carrying latent dihydrotetrazines were catalytically activated and covalently modified by trans-cyclooctene conjugates of small molecules, peptides, and proteins. In addition to visualization with fluorophores, fibers conjugated to a cell adhesive peptide exhibited a dramatically increased ability to mediate contact guidance of cells.

| S-EPMC4920269 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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