13094-51-4Relevant articles and documents
Matrix-assisted laser desorption/ionization mass spectrometry peptide sequencing utilizing selective N-terminal bromoacetylation
Song, Jinsu,Kim, Hie-Joon
, p. 269 - 276 (2012)
In tandem mass spectrometric peptide sequencing, simplifying the mass spectrum is often desirable. The b-series ions were distinguished from the y-series ions in the MALDI TOF-TOF spectra by incorporating a bromine-tag to the N-terminal amino group through rapid and selective acetylation using bromoacetic anhydride without blocking the lysine and tyrosine residues. The 51:49 ratio of Br-79 and Br-81 isotopes facilitated identification of ions carrying the tag. With the Br-tag in the b-series ions, N-terminal sequencing of tryptic peptides from hemoglobin as well as model peptides was straightforward. When the b-ions were low in intensity, ions without the Br-tag were identified as y-ions and used for sequencing.
Homogeneous and Robust Polyproline Type i Helices from Peptoids with Nonaromatic α-Chiral Side Chains
Roy, Olivier,Dumonteil, Geoffrey,Faure, Sophie,Jouffret, Laurent,Kriznik, Alexandre,Taillefumier, Claude
, p. 13533 - 13540 (2017)
Peptoids that are oligomers of N-substituted glycines represent a class of peptide mimics with great potential in areas ranging from medicinal chemistry to biomaterial science. Controlling the equilibria between the cis and trans conformations of their backbone amides is the major hurdle to overcome for the construction of discrete folded structures, particularly for the development of all-cis polyproline type I (PPI) helices, as tools for modulating biological functions. The prominent role of backbone to side chain electronic interactions (n → π) and side chains bulkiness in promoting cis-amides was essentially investigated with peptoid aromatic side chains, among which the chiral 1-naphthylethyl (1npe) group yielded the best results. We have explored for the first time the possibility to achieve similar performances with a sterically hindered α-chiral aliphatic side chain. Herein, we report on the synthesis and detailed conformational analysis of a series of (S)-N-(1-tert-butylethyl)glycine (Ns1tbe) peptoid homo-oligomers. The X-ray crystal structure of an Ns1tbe pentamer revealed an all-cis PPI helix, and the CD curves of the Ns1tbe oligomers also resemble those of PPI peptide helices. Interestingly, the CD data reported here are the first for any conformationally homogeneous helical peptoids containing only α-chiral aliphatic side chains. Finally we also synthesized and analyzed two mixed oligomers composed of NtBu and Ns1tbe monomers. Strikingly, the solid state structure of the mixed oligomer Ac-(tBu)2-(s1tbe)4-(tBu)2-COOtBu, the longest to be solved for any linear peptoid, revealed a PPI helix of great regularity despite the presence of only 50% of chiral side chain in the sequence.
Divergent and convergent synthesis of polymannosylated dibranched antigenic peptide of the immunodominant epitope MBP(83-99)
Friligou, Irene,Rizzolo, Fabio,Nuti, Francesca,Tselios, Theodore,Evangelidou, Maria,Emmanouil, Mary,Karamita, Maria,Matsoukas, John,Chelli, Mario,Rovero, Paolo,Papini, Anna Maria
, p. 6718 - 6725 (2013)
Multiple antigenic peptide (MAP) systems are dendrimeric structures bearing multiple copies of identical or different peptide epitopes, and they have been demonstrated to show enhanced immunogenicity. Herein, we report the direct (divergent) and indirect (convergent) synthesis, using contemporary synthetic approaches, of a di-branched antigenic peptide (di-BAP) containing the immunodominant epitope MBP(83-99), which is implicated in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). The direct synthesis (di-BAP 1) was performed using microwave irradiation. The indirect synthesis (di-BAP 2) was carried out performing an efficient chemoselective coupling reaction through the formation of a thioether bond. Both di-BAPs were conjugated to polysaccharide mannan since mannosylation is a promising technique to achieve modulation in immune response. The conjugation was achieved through free amino groups of both di-BAPs via the formation of Schiff bases. The mannan-conjugated di-BAPs were further evaluated in vivo in a prophylactic vaccination protocol, prior to EAE induction in Lewis rats.
An improved procedure for the synthesis of N-bromoacetyl-β- glycopyranosylamines, derivatives of mono- and disaccharides
Likhosherstov,Novikova,Zheltova,Shibaev
, p. 709 - 713 (2004)
An improved procedure for the synthesis of N-bromoacetyl-β- glycopyranosylamines from the corresponding β-glycosylamines was developed. The procedure is applicable to a wide range of derivatives of monosaccharides (hexoses, 2-acetamido-2-deoxyhexoses, hexuronamides, and 6-deoxyhexoses) and some disaccharides. For the derivatives of pentoses and 2-deoxyhexoses, the use of the corresponding β-glycosylammonium carbamates was found to be more convenient. N-Bromoacetyl-β-glycopyranosylamines derived from D-mannose, L-rhamnose, D-glucuronamide, 2-deoxy-D-arabino-hexose, 2-deoxy-D-lyxo-hexose, and melibiose were obtained for the first time.
Selection of fluorescent biosensors against galectin-3 from an NBD-modified phage library displaying designed α-helical peptides
Hashimoto, Masahiro,Miki, Takayuki,Chang, Iou Ven,Tsutsumi, Hiroshi,Mihara, Hisakazu
, (2021)
Fluorescent biosensors are indispensable tools for molecular imaging, detection, and drug screening. Conventionally, fluorescent biosensors were constructed by incorporating fluorophores into ligands. Here, to develop ligand-independent biosensors, we demonstrated biosensor selection from a fluorophore-modified peptide phage library. In this library, the peptides were designed to form α-helical structures, and one cysteine, the probe modification site, was located at the center of four randomized residues on the same face of the helix. By conjugation with 4-nitrobenzoxadiazole (NBD), we constructed an NBD-modified phage library. We conducted selection against galectin-3 (Gal-3), a galactose-specific lectin associated with various biological events such as tumor metastasis and insulin resistance. After biopanning, we obtained NBD-modified peptides that selectively bind to Gal-3 from the library. The fluorescence intensity of the hit biosensors increased with the concentration of Gal-3, and this fluorescent response was visually observed.
Synthetic approaches to macromolecular models for ion channel proteins
Azam, Farzana,Bladon, Christine M.
, p. 6377 - 6380 (1998)
The synthesis of a branched peptide is described using a ligation strategy to couple two peptides one of which is fully deprotected while the other is in a protected form. The ligation step involves formation of a thioether bond by using the thiol of a cysteine on the deprotected sequence to displace bromide from a bromoacetyl moiety on the second peptide.
Design, synthesis, and biological evaluation of CXCR4 ligands
Mona, Christine E.,Besserer-Offroy, élie,Cabana, Jér?me,Leduc, Richard,Lavigne, Pierre,Heveker, Nikolaus,Marsault, éric,Escher, Emanuel
, p. 10298 - 10311 (2016)
A combination of the CXCR4 inverse agonist T140 with N-terminal CXCL12 oligopeptides has produced the first nanomolar synthetic CXCR4 agonists. In these agonists, the inverse agonistic portion provides affinity whereas the N-terminal CXCL12 sequence induces receptor activation. Several CXCR4 crystal structures exist with either CVX15, an inverse agonist closely related to T140 and IT1t, a small molecule; we therefore attempted to produce another CXCL12 oligopeptide combination with IT1t. For this purpose, a primary amino group was introduced by total synthesis into one of the methyl groups of IT1t, serving as an anchoring point for the oligopeptide graft. The introduction of the oligopeptides on this analog however yielded antagonists, one compound displaying high affinity. On the other hand, the amino-substituted analogue itself proved to be an inverse agonist with a binding affinity of 2.6 nM compared to 11.5 nM for IT1t. This IT1t-like analog is hitherto one of the most potent non-peptidic CXCR4 inverse agonists reported.
Intra- and intermembrane pairwise molecular recognition between synthetic hydrogen-bonding phospholipids
Ma, Mingming,Paredes, Angel,Bong, Dennis
, p. 14456 - 14458 (2008)
Multivalency and preorganization are fundamental aspects of molecular recognition at the lipid membrane-water interface and can render weak monomeric binding interactions selective and robust; this concept is important throughout biology, biotechnology, and materials science. Though hydrogen bonding is typically weakened in water, intramembrane hydrogen bonding between native lipids has been well-studied and is thought to contribute to lipid bioactivity and membrane function. We hypothesized that avidity and preorganization effects at the lipid-water interface could overcome solvent competition and allow for selective hydrogen-bond recognition between small, unstructured components. We have found that electrostatically identical vesicular membranes composed of cyanuric acid and melamine functionalized phospholipids 1 and 2 undergo selective apposition, fusion and adhesion in suspension and on solid support, indicating that their well-known low-dielectric hydrogen bonding properties translate effectively to the lipid-water interface. This work is notable and of general interest given the few detailed studies of aqueous phase hydrogen-bonding systems; we have extensively characterized this system, gaining structural, functional, and thermodynamic data. Furthermore, we have found that the designed lipid-lipid headgroup interactions result in dramatic alteration of the lipid phase morphology, providing insight into the coupling of molecular interactions with assembly state. As such, this work contributes to our understanding of fundamental phenomena such as molecular recognition at the lipid-water interface membrane chemistry and further illustrates the general possibility of designing selective hydrogen-bonding adhesive interactions from simple starting materials at other polar-apolar interfaces; this could have numerous materials and biotechnological applications. Copyright
CHROMOGENIC PEROXIDASE SUBSTRATES
-
Paragraph 0412, (2017/07/14)
Chromogenic conjugates for color-based detection of targets are described. The conjugates comprise a chromogenic moiety such as rhodamine, rhodol or fluorescein. The chromogenic moiety is linked to a peroxidase substrate. The chromogenic conjugates can be used in immunohistochemical analysis and in situ hybridization. The conjugates can be used to detect 1, 2, 3 or more targets in a sample by color.
Development of cyclic peptomer inhibitors targeting the polo-box domain of polo-like kinase 1
Murugan, Ravichandran N.,Park, Jung-Eun,Lim, Dan,Ahn, Mija,Cheong, Chaejoon,Kwon, Taeho,Nam, Ky-Youb,Choi, Sun Ho,Kim, Bo Yeon,Yoon, Do-Young,Yaffe, Michael B.,Yu, Dae-Yeul,Lee, Kyung S.,Bang, Jeong Kyu
, p. 2623 - 2634 (2013/06/27)
The polo-box domain (PBD) of polo-like kinase 1 (Plk1) is essentially required for the function of Plk1 in cell proliferation. The availability of the phosphopeptide-binding pocket on PBD provides a unique opportunity to develop novel protein-protein interaction inhibitors. Recent identification of a minimal 5-residue-long phosphopeptide, PLHSpT, as a Plk1 PBD-specific ligand has led to the development of several peptide-based inhibitors, but none of them is cyclic peptide. Through the combination of single-peptoid mimics and thio-ether bridged cyclization, we successfully demonstrated for the first time two cyclic peptomers, PL-116 and PL-120, dramatically improved the binding affinity without losing mono-specificity against Plk1 PBD in comparison with the linear parental peptide, PLHSpT. These cyclic peptomers could serve as promising templates for future drug designs to inhibit Plk1 PBD.
