4960-81-0Relevant academic research and scientific papers
Engineering of a Potent, Long-Acting NPY2R Agonist for Combination with a GLP-1R Agonist as a Multi-Hormonal Treatment for Obesity
Lear, Sam,Pflimlin, Elsa,Zhou, Zhihong,Huang, David,Weng, Sharon,Nguyen-Tran, Van,Joseph, Sean B.,Roller, Shane,Peterson, Scott,Li, Jing,Tremblay, Matthew,Schultz, Peter G.,Shen, Weijun
, p. 9660 - 9671 (2020)
Bariatric surgery results in increased intestinal secretion of hormones GLP-1 and anorexigenic PYY, which is believed to contribute to the clinical efficacy associated with the procedure. This observation raises the question whether combination treatment with gut hormone analogs might recapitulate the efficacy and mitigate the significant risks associated with surgery. Despite PYY demonstrating excellent efficacy and safety profiles with regard to food intake reduction, weight loss, and glucose control in preclinical animal models, PYY-based therapeutic development remains challenging given a low serum stability and half-life for the native peptide. Here, combined peptide stapling and PEG-fatty acid conjugation affords potent PYY analogs with >14 h rat half-lives, which are expected to translate into a human half-life suitable for once-weekly dosing. Excellent efficacy in glucose control, food intake reduction, and weight loss for lead candidate 22 in combination with our previously reported long-acting GLP-1 analog is demonstrated in a diet-induced obesity mouse model.
Selective and broad spectrum amphiphilic small molecules to combat bacterial resistance and eradicate biofilms
Hoque, Jiaul,Konai, Mohini M.,Samaddar, Sandip,Gonuguntala, Spandhana,Manjunath, Goutham B.,Ghosh, Chandradhish,Haldar, Jayanta
, p. 13670 - 13673 (2015)
Rationally designed amphiphilic small molecules selectively kill drug-sensitive and drug-resistant bacteria over mammalian cells. The small molecules disperse preformed biofilms and reduce viable bacterial count in the biofilms. Moreover, this class of me
Synthesis and Aggregation of Novel Sugar-Based Gemini Surfactant with a N, N′-Acetylethylenediamine Spacer in Aqueous Solution
Wang, Ruijuan,WanYan, Ruihua,Yang, Shuo,Wang, Dong,Yin, Zhigang
, p. 697 - 703 (2020)
A novel sugar-based Gemini surfactant with a N,N′-acetylethylenediamine spacer (N,N′ (N-dodecyl-2-D-glucosaminyl acetyl) ethylenediamine, Glu(12)-(AA)-Glu(12)), was synthesized with D-(+)-Glucono-1,5-lactone as starting material in three steps. The surfactant's structure was confirmed using 1H and 13C nuclear magnetic resonance (NMR) spectroscopy and electrospray ionization mass spectrometry (ESI-MS). The aggregation behavior of Glu(12)-(AA)-Glu(12) in aqueous solution at pH 4.0, 7.0, and 10.0 was investigated by surface tension, dynamic light scattering (DLS), and cryogenic transmission electron microscopic (Cryo-TEM) measurements. The surface tension measurement shows that the critical micelle concentration (CMC) of Glu(12)-(AA)-Glu(12) is at the concentration level of 10?5 mol·L?1 at 25 °C, which is significantly lower than that of corresponding monomeric sugar-based surfactants. Compared with such sugar-based Gemini surfactants with similar hydrophilic spacers, Glu(12)-(AA)-Glu(12) demonstrated similar or slightly lower surface activity. The CMC value of Glu(12)-(AA)-Glu(12) underwent a slight decrease with the increase of pH. DLS and Cryo-TEM measurements reveal that Glu(12)-(AA)-Glu(12) forms micelles at acidic pH (pH 4.0) and the micelles are transformed into vesicles at neutral or high pH (pH 7.0, 10.0). The microstructural transformation of Glu(12)-(AA)-Glu(12) aggregates is related to the protonation state of its two tertiary amines in the head groups versus pH.
PEPTIDE CONJUGATES AND METHODS OF USE
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Paragraph 0368, (2021/06/11)
Peptide conjugates comprising a peptide selected from a peptide that modulates the PYY receptor, a peptide that modulates both the GLP-1 receptor and the GCG receptor, a peptide that modulates both the GLP-1 receptor and the GIP receptor, and a peptide that modulates the GLP-1 receptor; and a staple attached to the peptide at a first amino acid and a second amino acid are disclosed herein. Also provided are peptide conjugates comprising prolactin-releasing peptide. The peptide conjugates may be used for treating conditions such as obesity. Further provided are stapled prolactin-releasing peptide.
DIMER COMPOUNDS, AND USE IN BINDING TOXIC REPEATS OF RNA
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Paragraph 0249; 0254, (2020/07/16)
Provided herein are compounds and methods for modulating abnormal repeat expansions of gene sequences. More particularly, provided are dimeric inhibitors of RNA and the uses of such inhibitors in regulating nucleotide repeat expansions, e.g., to treat Myotonic Dystrophy Type 1 (DM1), Myotonic Dystrophy Type 2 (DM2), Fuchs dystrophy, Huntington Disease, Amyotrophic Lateral Sclerosis, or Frontotemporal Dementia.
COLLECTIONS OF PEPTIDES, PEPTIDE AGENTS, AND METHODS OF USE THEREOF
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Paragraph 0340-0341, (2020/03/15)
The present disclosure provides powerful technologies for the development, production, characterization, and/or use of stapled peptide compositions. Among other things, the present disclosure provides strategies for defining amino acid sequences particularly amenable or useful for stapling, as well as technologies, reagents, and systems for developing, producing, characterizing, and/or using stapled peptides having such amino acid sequences.
HEMIAMINAL-TAG FOR PROTEIN LABELING AND PURIFICATION
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Page/Page column 17, (2018/06/30)
The invention pertains to the synthesis, isolation, and characterization of hemiaminal for selective labeling of peptides, proteins, antibodies, and organic fragments with -C(=0) CH2NH2 and derivatives with -CH2NH2 group over -C(=0) CHRNH2 group (where R≠H). The invention also pertains to the method of single-site immobilization of proteins through N-terminus Gly on solid phase. The invention includes late-stage tagging of N-terminus Gly with an affinity tag, 19F NMR probe, and a fluorophore and a method for metal-free protein purification and isolation of analytically pure proteins.
ANTIBODIES CAPABLE OF SPECIFICALLY BINDING TWO EPITOPES ON TISSUE FACTOR PATHWAY INHIBITOR
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Paragraph 0523; 0524, (2016/02/23)
The application discloses a combination of two monospecific TFPI antibodies, wherein one antibody is capable of specifically binding TFPI (1-181) and the other antibody is capable of specifically binding TFPI (182-276), as well as bispecific anti-TFPI antibodies derived from two such monospecific antibodies. Both the combination of the two monospecific antibodies and the bispecific antibody strongly enhance thrombin generation by neutralising full length TFPIα, even where the concentration of TFPI is abnormally elevated.
Membrane Active Small Molecules Show Selective Broad Spectrum Antibacterial Activity with No Detectable Resistance and Eradicate Biofilms
Hoque, Jiaul,Konai, Mohini M.,Gonuguntla, Spandhana,Manjunath, Goutham B.,Samaddar, Sandip,Yarlagadda, Venkateswarlu,Haldar, Jayanta
, p. 5486 - 5500 (2015/08/03)
Treating bacterial biofilms with conventional antibiotics is limited due to ineffectiveness of the drugs and higher propensity to develop bacterial resistance. Development of new classes of antibacterial therapeutics with alternative mechanisms of action has become imperative. Herein, we report the design, synthesis, and biological evaluations of novel membrane-active small molecules featuring two positive charges, four nonpeptidic amide groups, and variable hydrophobic/hydrophilic (amphiphilic) character. The biocides synthesized via a facile methodology not only displayed good antibacterial activity against wild-type bacteria but also showed high activity against various drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), and β-lactam-resistant Klebsiella pneumoniae. Further, these biocides not only inhibited the formation of biofilms but also disrupted the established S. aureus and E. coli biofilms. The membrane-active biocides hindered the propensity to develop bacterial resistance. Moreover, the biocides showed negligible toxicity against mammalian cells and thus bear potential to be used as therapeutic agents.
Synthesis of cyclic functionalized bisulfides and their oligomers
Bonnans-Plaisance,Levesque,Toulin
, p. 231 - 244 (2007/10/03)
In order to obtain comonomers for the free-radical polymerization of acrylic or vinylic monomers, cyclic disufides were synthesized. Ester or amide functions were introduced in these cyclic molecules in order to afford easily degradable centers in the cop
