- Alaninyl variants of the marine natural product halocyamine A and their antibacterial properties
-
In an effort to explore the antibacterial potential of the marine natural product halocyamine A, a series of analogues including desbromo and alanine-substituted variants were synthesised and evaluated for biological activity against a panel of Gram-positive and –negative bacteria. The analogues were synthesised by a combination of solid-phase peptide synthesis and ruthenium complex/ytterbium triflate catalysed hydroamidation chemistry. Single alanine substitutions ([Ala1]-halocyamine A and [Ala2]-halocyamine A) gave only modest increases in activity towards Gram-positive bacteria, while di-alaninyl variants exhibited more potent activity with MIC values of 12.5–50 μM towards the Gram-positive bacteria Staphylococcus aureus and Enterococcus faecalis. A lipophilic trityl-protected intermediate of [Ala2]-halocyamine was the most active against the Gram-negative bacterium Escherichia coli.
- Fong, Hugo K.H.,Cadelis, Melissa M.,Brunel, Jean Michel,Bourguet-Kondracki, Marie-Lise,Barker, David,Copp, Brent R.
-
-
Read Online
- Benzoisothiazolone (BIT): A Fast, Efficient, and Recyclable Redox Reagent for Solid Phase Peptide Synthesis
-
Solid-phase peptide synthesis (SPPS), a preferred synthetic procedure, generates by-products and effluents in multiple equivalents for one equivalent of desired product. Presented herein is the use of a fast and efficient coupling protocol for SPPS using a benzoisothiazolone (BIT), which can be fully recycled. The BIT, as redox activator, works under very mild conditions and generates minimal amount of waste. As a case study, the BIT coupling protocol is applied to the synthesis of side chain of the recently discovered antibiotic, teixobactin.
- Bukya, Hemalatha,Gangireddy, Pavankumar,Mainkar, Prathama S.,Nayani, Kiranmai
-
supporting information
p. 5358 - 5362
(2020/08/27)
-
- ANTI-EGFR ANTIBODY DRUG CONJUGATES
-
The invention relates to anti-Epidermal Growth Factor Receptor (EGFR) antibody drug conjugates (ADCs) which inhibit Bcl-xL, including compositions and methods of using said ADCs.
- -
-
Paragraph 0936
(2019/06/07)
-
- ANTI-CD98 ANTIBODIES AND ANTIBODY DRUG CONJUGATES
-
The invention relates to anti-CD98 antibodies and antibody drug conjugates (ADCs), including compositions and methods of using said antibodies and ADCs.
- -
-
Page/Page column 296
(2018/01/15)
-
- SPECIFICALLY ACTIVATED MICROMOLECULAR TARGET COUPLING BODY IN TUMOR MICROENVIRONMENT AND USE THEREOF
-
Provided are an anticancer compound comprising a cleavable linker specifically activated in a tumor microenvironment, and use thereof. The anticancer compound is represented by the following formula, wherein, R1 is a normal functional group or a protection group; R2 is Ala, Thr, Val or Ile; R3 is Ala, Val or Asn; R4 is a drug group linked via a hydroxyl group or an amino group; and the general formula of the drug is R4H. The anticancer compound is only activated at a local portion of a tumor, thus avoiding the defect of immune system damage of a traditional chemotherapeutic drug, and promoting tumor immunization by removing a tumor immunosuppression cell. The anticancer compound or pharmaceutical composition thereof is jointly used with immunotherapy, thus improving the effect of treating the tumor, and effectively inhibiting tumor metastasis and osseous metastasis.
- -
-
Paragraph 0265
(2017/07/14)
-
- Localized Supramolecular Peptide Self-Assembly Directed by Enzyme-Induced Proton Gradients
-
Electrodes are ideal substrates for surface localized self-assembly processes. Spatiotemporal control over such processes is generally directed through the release of ions generated by redox reactions occurring specifically at the electrode. The so-used gradients of ions proved their effectiveness over the last decade but are in essence limited to material-based electrodes, considerably reducing the scope of applications. Herein is described a strategy to enzymatically generate proton gradients from non-conductive surfaces. In the presence of oxygen, immobilization of glucose oxidase (GOx) on a multilayer film provides a flow of protons through enzymatic oxidation of glucose by GOx. The confined acidic environment located at the solid–liquid interface allows the self-assembly of Fmoc-AA-OH (Fmoc=fluorenylmethyloxycarbonyl and A=alanine) dipeptides into β-sheet nanofibers exclusively from and near the surface. In the absence of oxygen, a multilayer nanoreactor containing GOx and horseradish peroxidase (HRP) similarly induces Fmoc-AA-OH self-assembly.
- Rodon Fores, Jennifer,Martinez Mendez, Miguel Leonardo,Mao, Xiyu,Wagner, Déborah,Schmutz, Marc,Rabineau, Morgane,Lavalle, Philippe,Schaaf, Pierre,Boulmedais, Fouzia,Jierry, Lo?c
-
supporting information
p. 15984 - 15988
(2017/11/22)
-
- Maytansinoid derivatives with peptide linker and conjugates thereof
-
The invention relates to novel cell-binding agent-cytotoxic agent conjugate having a peptide linkers and more specifically to conjugates of formula (I). The invention also provides novel cytotoxic agents of formula (II), linker compounds represented by fo
- -
-
Page/Page column 111; 112
(2016/04/20)
-
- ANTIBODY DRUG CONJUGATES WITH CELL PERMEABLE BCL-XL INHIBITORS
-
Small molecule Bcl-xL inhibitors and Antibody Drug Conjugates (ADCs) comprising small molecule Bcl-xL inhibitors are disclosed herein. The Bcl-xL inhibitors and ADCs of the disclosure are useful for, among other things, inhibiting anti-apoptotic Bcl xL proteins as a therapeutic approach towards the treatment of diseases that involve a dysregulated apoptosis pathway.
- -
-
Paragraph 000457
(2016/07/05)
-
- PEPTIDE-DRUG CONJUGATES
-
Peptide-drug conjugates comprising p-aminobenzyl carbamoyl or p-aminobenzolyl carbonate self-immolating linkers are disclosed. The peptide-drug conjugates comprise a peptide moiety that can be cleaved by cellular proteases, bound to the self-immolating li
- -
-
Page/Page column 22; 23
(2016/01/22)
-
- Two-fold odd-even effect in self-assembled nanowires from oligopeptide-polymer-substituted perylene bisimides
-
Organic nanowires are important building blocks for nanoscopic organic electronic devices. In order to ensure efficient charge transport through such nanowires, it is important to understand in detail the molecular parameters that guide self-assembly of π-conjugated molecules into one-dimensional stacks with optimal constructive π-π overlap. Here, we investigated the subtle relationship between molecular structure and supramolecular arrangement of the chromophores in self-assembled nanowires prepared from perylene bisimides with oligopeptide-polymer side chains. We observed a two-fold odd-even effect in circular dichroism spectra of these derivatives, depending on both the number of l-alanine units in the oligopeptide segments and length of the alkylene spacer between chromophore and oligopeptide substituents. Our results indicate that there is a complex interplay between the translation of molecular chirality into supramolecular helicity and the molecules' inherent propensity for well-defined one-dimensional aggregation into β-sheet-like superstructures in the presence of a central chromophore. Strong excitonic coupling as expressed by the appearance of hypsochromically and bathochromically shifted UV-vis absorptions and strong CD signals was systematically observed for molecules with an odd number of l-alanines in the side chains. The latter derivatives gave rise to nanowires with a significantly higher electron mobility. Our results, hence, provide an important design rule for self-assembled organic nanowires.
- Marty, Roman,Nigon, Robin,Leite, Deborah,Frauenrath, Holger
-
supporting information
p. 3919 - 3927
(2014/04/03)
-
- Microwave irradiated high-speed solution synthesis of peptide acids employing Fmoc-amino acid pentafluorophenyl esters as coupling agents
-
A high-speed solution phase synthesis of peptide acids employing commercially available Fmoc-amino acid pentafluorophenyl esters as coupling agents has been demonstrated. The coupling has been found to be fast and completed in 30-45 sec. A simple work-up of the reaction mixture has resulted N-protected peptide acids in good yield. Utilizing the present method, the coupling of difficult sequences containing highly hindered α, α-dialkyl amino acids has also been demonstrated. Further, the synthesis of diastereomeric dipeptides, Fmoc-Phg-Phe-OMe and Fmoc-D-Phg-Phe-OMe revealed that the coupling is free from racemization.
- Suresh Babu, Vommina V.,Ramana Rao
-
p. 2328 - 2332
(2007/10/03)
-
- Supramolecular Hydrogels Respond to Ligand-Receptor Interaction
-
N-(Fluorenyl-9-Methoxycarbonyl) dipeptides form supramolecular hydrogels via hydrogen bonding and hydrophobic interactions. These hydrogels respond to a ligand?receptor interaction as well as to thermal or pH perturbation and also exhibit chiral recognition. Copyright
- Zhang, Yan,Gu, Hongwei,Yang, Zhimou,Xu, Bing
-
p. 13680 - 13681
(2007/10/03)
-
- Synthesis and in vitro enzyme activity of peptide derivatives of bacterial cell wall biosynthesis inhibitors
-
The enzyme diaminopimelate aminotransferase (DAP-AT) is a good potential target for the design of novel antibacterial agents. We have synthesised a series of peptide hydrazines based on the structure of the natural substrate of DAP-AT. These compounds show varied inhibition properties in vitro vs. DAP-AT from E. coli as well as moderate antimicrobial activity vs. E. coli. Examination of the kinetics of inhibition reveals that hydrazine, as well as the substituted hydrazino-peptides, shows two-phase slow-binding inhibition. Possible mechanisms for inhibition are discussed. The Royal Society of Chemistry 2000.
- Cox, Russell J.,Jenkins, Helen,Schouten, James A.,Stentiford, Rosie A.,Wareing, Katrina J.
-
p. 2023 - 2036
(2007/10/03)
-
