156939-66-1Relevant articles and documents
Rational Design of Right-Handed Heterogeneous Peptidomimetics as Inhibitors of Protein-Protein Interactions
Shi, Yan,Sang, Peng,Lu, Junhao,Higbee, Pirada,Chen, Lihong,Yang, Leixiang,Odom, Timothy,Daughdrill, Gary,Chen, Jiandong,Cai, Jianfeng
, p. 13187 - 13196 (2020)
Peptidomimetics have gained great attention for their function as protein-protein interaction (PPI) inhibitors. Herein, we report the design and investigation of a series of right-handed helical heterogeneous 1:1 α/Sulfono-I-AA peptides as unprecedented inhibitors for p53-MDM2 and p53-MDMX. The most potent helical heterogeneous 1:1 α/Sulfono-I-AA peptides were shown to bind tightly to MDM2 and MDMX, with Kd of 19.3 and 66.8 nM, respectively. Circular dichroism spectra, 2D-NMR spectroscopy, and the computational simulations suggested that these helical sulfono-I-AA peptides could mimic the critical side chains of p53 and disrupt p53/MDM2 PPI effectively. It was noted that these 1:1 α/Sulfono-I-AA peptides were completely resistant to proteolytic degradation, boosting their potential for biomedical applications. Furthermore, effective cellular activity is achieved by the stapled 1:1 α/Sulfono-I-AA peptides, evidenced by significantly enhanced p53 transcriptional activity and much more induced level of MDM2 and p21. The 1:1 α/Sulfono-I-AA peptides could be an alternative strategy to antagonize a myriad of PPIs.
Triazolo-peptidomimetics: novel radiolabeled minigastrin analogs for improved tumor targeting
Grob, Nathalie M.,H?ussinger, Daniel,Deupi, Xavier,Schibli, Roger,Behe, Martin,Mindt, Thomas L.
supporting information, p. 4484 - 4495 (2020/06/08)
MG11 is a truncated analog of minigastrin, a peptide with high affinity and specificity toward the cholecystokinin-2 receptor (CCK2R), which is overexpressed by different tumors. Thus, radiolabeled MG11 derivatives have great potential for use in cancer d
Synthesis and biological activity of peptide α-ketoamide derivatives as proteasome inhibitors
Pacifico, Salvatore,Ferretti, Valeria,Albanese, Valentina,Fantinati, Anna,Gallerani, Eleonora,Nicoli, Francesco,Gavioli, Riccardo,Zamberlan, Francesco,Preti, Delia,Marastoni, Mauro
supporting information, p. 1086 - 1092 (2019/08/01)
Proteasome activity affects cell cycle progression as well as the immune response, and it is largely recognized as an attractive pharmacological target for potential therapies against several diseases. Herein we present the synthesis of a series of pseudo
Somatostatin-Dopamine Chimeric Analogs
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Paragraph 0326, (2015/11/17)
The present invention relates to novel somatostatin-dopamine chimeric analogs and their therapeutic uses for the inhibition, prevention, and/or treatment of neoplasia, neuroendocrine tumors, Cushing's disease/syndrome, and other conditions.
1,2,3-Triazole Stabilized Neurotensin-Based Radiopeptidomimetics for Improved Tumor Targeting
Mascarin, Alba,Valverde, Ibai E.,Vomstein, Sandra,Mindt, Thomas L.
, p. 2143 - 2152 (2015/11/09)
Neurotensin (NT) is a regulatory peptide with nanomolar affinity toward NT receptors, which are overexpressed by different clinically relevant tumors. Its binding sequence, NT(8-13), represents a promising vector for the development of peptidic radiotracers for tumor imaging and therapy. The main drawback of the peptide is its short biological half-life due to rapid proteolysis in vivo. Herein, we present an innovative strategy for the stabilization of peptides using nonhydrolizable 1,4-disubstituted, 1,2,3-triazoles as amide bond surrogates. A triazole scan?of the peptide sequence yielded novel NT(8-13) analogues with enhanced stability, retained receptor affinity, and improved tumor targeting properties in vivo. The synthesis of libraries of triazole-based peptidomimetics was achieved efficiently on solid support by a combination of Fmoc-peptide chemistry, diazo transfer reactions, and the Cu(I)-catalyzed alkyne azide cycloaddition (CuAAC) employing methods that are fully compatible with standard solid phase peptide synthesis (SPPS) chemistry. Thus, the amide-to-triazole substitution strategy may represent a general methodology for the metabolic stabilization of biologically active peptides.
Synthesis of α, β-unsaturated γ-amino esters with unprecedented high (E)-stereoselectivity and their conformational analysis in peptides
Mali, Sachitanand M.,Bandyopadhyay, Anupam,Jadhav, Sandip V.,Kumar, Mothukuri Ganesh,Gopi, Hosahudya N.
supporting information; experimental part, p. 6566 - 6574 (2011/11/05)
Mild, efficient and racemization-free synthesis of N-protected α, β-unsaturated γ-amino esters with unprecedented high E- stereoselectivity is described. This method is found to be compatible with Boc-, Fmoc- and other side chain protecting groups. The crystal conformations of the vinylogous γ-amino esters in monomers and in homo- and mixed dipeptides are studied. Further, the vinylogous homo-dipeptide showed a β-sheet conformation, while mixed α- and α,β-unsaturated γ-hybrid dipeptide adapted an irregular structure in single crystals.
Solid-phase synthesis and screening of N-acylated polyamine (NAPA) combinatorial libraries for protein binding
Iera, Jaclyn A.,Jenkins, Lisa M. Miller,Kajiyama, Hiroshi,Kopp, Jeffrey B.,Appella, Daniel H.
supporting information; experimental part, p. 6500 - 6503 (2011/02/16)
Inhibitors for protein-protein interactions are challenging to design, in part due to the unique and complex architectures of each protein's interaction domain. Most approaches to develop inhibitors for these interactions rely on rational design, which re
POLYAMINE COMPOUNDS THAT BIND TAR RNA OF HIV AND METHODS OF TREATING VIRAL DISORDERS
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Page/Page column 36-37, (2009/12/27)
The invention provides for novel polyamine compounds, substituted at the side chains, which can treat various disease states including viral infection, e.g. HIV infection, at low cytotoxicity values.
ETHOID-CONTAINING COMPOUNDS, METHODS FOR PREPARING ETHOID-CONTAINING COMPOUNDS, AND METHODS FOR USE
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Page/Page column 179, (2008/12/05)
Ethoid-containing compounds comprising one or more ethoid moieties (e.g., a methyleneoxy, Ψ[CH2O]) as a substitutive, isosteric replacement for an amide moiety of a polyaminoacid are disclosed. Universal, modular approaches for preparing such ethoid-containing compounds are also disclosed. Such ethoid-containing compounds can be polyaminoacid analogs, and are useful as food additives, as cosmetics ingredients, as research reagents, as diagnostic agents, and as therapeutic agents.
Nonionic side chains modulate the affinity and specificity of binding between functionalized polyamines and structured RNA
Lawton, Graham R.,Appella, Daniel H.
, p. 12762 - 12763 (2007/10/03)
This Communication introduces side-chain-bearing polyamines as molecules for selective recognition of folded RNA structures. The complex folded structures associated with RNA create binding pockets for proteins, and also binding sites for small molecules.