1418009-93-4

Usage

Chemical Properties

White crystalline powder

Upstream product

• 13734-28-6 Boc-Lys-OH 
• 846549-33-5 dicyclohexylammonium N-tert-butyloxycarbonyl-2-amino-6-azidohexanoate 
• 846549-33-5 Boc-Lys(ε-azide)-OH 
• 51790-14-8 L-tryptophanyl-L-lysine 
• 468065-37-4 methyl 6-azido-2-(boc-amino)hexanoate 
• 55757-60-3 N-α-(tert-butoxycarbonyl)-L-lysine methyl ester 
• 73548-77-3 Boc-L-Lys(Z)-OMe 
• 2389-45-9 Boc-Lys(Z)-OH 
• 159610-91-0 methyl-(S)-2-amino-6-azidohexanoate 
• 161264-05-7 (2R)-N-<<>(2S)-2-<amino>-6-iodohexan-1-oyl>bornane-10,2-sultam 

Relevant academic research and scientific papers

Site-specifically phosphorylated lysine peptides

Protein phosphorylation controls major processes in cells. Although phosphorylation of serine, threonine, and tyrosine and also recently histidine and arginine are well-established, the extent and biological significance of lysine phosphorylation has remained elusive. Research in this area has been particularly limited by the inaccessibility of peptides and proteins that are phosphorylated at specific lysine residues, which are incompatible with solid-phase peptide synthesis (SPPS) due to the intrinsic acid lability of the P(=O)-N phosphoramidate bond. To address this issue, we have developed a new synthetic route for the synthesis of site-specifically phospholysine (pLys)-containing peptides by employing the chemoselectivity of the Staudinger-phosphite reaction. Our synthetic approach relies on the SPPS of unprotected ε-azido lysine-containing peptides and their subsequent reaction to phosphoramidates with phosphite esters before they are converted into the natural modification via UV irradiation or basic deprotection. With these peptides in hand, we demonstrate that electron-transfer dissociation tandem mass spectrometry can be used for unambiguous assignment of phosphorylated-lysine residues within histone peptides and that these peptides can be detected in cell lysates using a bottom-up proteomic approach. This new tagging method is expected to be an essential tool for evaluating the biological relevance of lysine phosphorylation.

Chemoselective Nitrile Oxide-Alkyne 1,3-Dipolar Cycloaddition Reactions from Nitroalkane-Tethered Peptides

Synthesis and incorporation of a new amino acid with a nitroalkane side chain into peptides, in situ transformation of a nitroalkane side chain into nitrile oxide, and chemoselective 1,3-dipolar cycloaddition reactions between in situ generated nitrile oxide and different alkynes are reported. The nitroalkane-mediated nitrile oxide-alkyne cycloaddition was found to be orthogonal to the copper(I)-catalyzed azide-alkyne cycloaddition reaction. The combination of orthogonal nitrile oxide-alkyne and azide-alkyne cycloaddition reactions can be explored to tailor different 1,2,3-triazole and 3,5-isoxazoles, respectively, on the peptide backbone.

COMPOUNDS AND METHODS FOR SELECTIVE C-TERMINAL LABELING

The present disclosure relates to compounds and methods for selective C-terminal functionalization of peptides. In certain embodiments, the compounds have improved water-solubility, and are suitable for use in connection with peptide sequencing methodologies.

A Versatile Approach for Site-Specific Lysine Acylation in Proteins

Using amber suppression in coordination with a mutant pyrrolysyl-tRNA synthetase-tRNAPylpair, azidonorleucine is genetically encoded in E. coli. Its genetic incorporation followed by traceless Staudinger ligation with a phosphinothioester allows the convenient synthesis of a protein with a site-specifically installed lysine acylation. By simply changing the phosphinothioester identity, any lysine acylation type could be introduced. Using this approach, we demonstrated that both lysine acetylation and lysine succinylation can be installed selectively in ubiquitin and synthesized histone H3 with succinylation at its K4 position (H3K4su). Using an H3K4su-H4 tetramer as a substrate, we further confirmed that Sirt5 is an active histone desuccinylase. Lysine succinylation is a recently identified post-translational modification. The reported technique makes it possible to explicate regulatory functions of this modification in proteins.

HOMOMULTIVALENT AND HETEROMULTIVALENT INHIBITORS OF PROSTATE SPECIFIC MEMBRANE ANTIGEN (PMSA) AND USES THEREOF

The present invention provides bivalent and multivalent ligands with a view to improving the affinity and pharmacokinetic properties of a urea class of PSMA inhibitors. The compounds and their synthesis can be generalized to multivalent compounds of other target antigens. Because they present multiple copies of the pharmacophore, multivalent ligands can bind to receptors with high avidity and affinity, thereby serving as powerful inhibitors. The modular multivalent scaffolds of the present invention, in one or more embodiments, contains a lysine-based (α-, ε-) dialkyne residue for incorporating two or more antigen binding moieties, such as PSMA binding Lys-Glu urea moieties, exploiting click chemistry and one or more additional lysine residues for subsequent modification with an imaging and/or therapeutic nuclides or a cytotoxic ligands for tumor cell killing.

PSMA-TARGETING COMPOUNDS AND USES THEREOF

Prostate-specific membrane antigen (PSMA) targeting compounds are described. Uses of the compounds for imaging, therapy, cell sorting, and tumor mapping are also described.

Nα-Fmoc-protected ω-azido- and ω-alkynyl-L- amino acids as building blocks for the synthesis of "clickable" peptides

The growing interest in the 1,4-disubstituted-1,2,3-triazolyl moiety as an amide bond surrogate and its formation through very mild, chemoselective, and bioorthogonal CuI-catalyzed Huisgen 1,3-dipolar [3+2] cycloaddition of an alkynyl to an azi

Presentation and detection of azide functionality in bacterial cell surface proteins

An improved protocol for copper-catalyzed triazole formation on the bacterial cell surface is described. Addition of highly pure CuBr to cells treated with azidohomoalanine (2) leads to ca. 10-fold more extensive cell surface labeling than previously observed. This highly active catalyst allows detection of the methionine analogues azidoalanine (1), azidonorvaline (3), and azidonorleucine (4) in cell surface proteins. Azidoalanine was previously believed to be silent with regard to the cellular protein synthesis machinery.

Single chain peptide compounds having hemoregulatory activity

There is disclosed single chain peptide compounds, substituted at a Cα-atom of a non-terminal amino acid by a group--A which is defined in claim 1. The native α-side chain of the Cα atom bonded group to group --A absent. The peptide derivatives according

Asymmetric alkylations of a sultam-derived glycine equivalent: Practical preparation of enantiomerically pure α-amino acids

Alkylation of the chiral glycine derivative 2 with 'activated' organohalides under ultrasound-assisted phase-transfer catalysis or with activated and nonactivatcd organohalides in anhydrous medium provides (mostly crystalline) alkylation products 3. Acidic hydrolysis of the pure products 3 gives (aminoacyl)sultams 4 which by mild saponification furnish pure α-amino acids 5 in good overall yields from 2, along with recovered auxiliary 1 (Scheme 1). Pure ω-protected α,ω-diamino acids and α-amino-ω-(hydroxyamino)acids 12-16 are readily accessible from (ω-haloacyl)sultams 3 via reaction with N-nucleophiles followed by acidic and basic hydrolyses (Scheme 2). A reliable determination of the enantiomeric purity of α-amino acids using HPLC analysis of their N-(3,5-dinitrobenzoyl)prolyl derivatives 17 is presented.