132622-65-2Relevant articles and documents
Potent and Selective Conformationally Restricted Neuronal Nitric Oxide Synthase Inhibitors
Gómez-Vidal, José A.,Martásek, Pavel,Roman, Linda J.,Silverman, Richard B.
, p. 703 - 710 (2004)
Selective inhibition of the isoforms of nitric oxide synthase (NOS) in pathologically elevated synthesis of nitric oxide has great therapeutic potential. We previously reported nitroarginine-containing dipeptide amides (Huang, H.; Martasek, P.; Roman, L.
Multipodal insulin mimetics built on adamantane or proline scaffolds
Hajduch, Jan,Fabre, Benjamin,Klopp, Benjamin,Pohl, Radek,Budě?ínsky, Milo?,?olínová, Veronika,Ka?i?ka, Václav,K?prülüoglu, Cemal,Eyrilmez, Saltuk Mustafa,Lep?ík, Martin,Hobza, Pavel,Mitrová, Katarína,Lubos, Marta,Hernández, María Soledad Garre,Jirá?ek, Ji?í
, (2020/12/29)
Multi-orthogonal molecular scaffolds can be applied as core structures of bioactive compounds. Here, we prepared four tri-orthogonal scaffolds based on adamantane or proline skeletons. The scaffolds were used for the solid-phase synthesis of model insulin mimetics bearing two different peptides on the scaffolds. We found that adamantane-derived compounds bind to the insulin receptor more effectively (Kd value of 0.5 μM) than proline-derived compounds (Kd values of 15–38 μM) bearing the same peptides. Molecular dynamics simulations suggest that spacers between peptides and central scaffolds can provide greater flexibility that can contribute to increased binding affinity. Molecular modeling showed possible binding modes of mimetics to the insulin receptor. Our data show that the structure of the central scaffold and flexibility of attached peptides in this type of compound are important and that different scaffolds should be considered when designing peptide hormone mimetics.
A inhibiting DPP-IV compounds and intermediates
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, (2016/10/20)
Provided are compounds as presented in formulas IA or IB or pharmaceutically acceptable salts thereof, the preparation method therefor, and uses thereof. Also provided are the intermediates of the compounds and the preparation method therefor. The compounds of the present invention can effectively inhibit DPP-IV activity. Compared to the commercial available medicine, Januvia, compound 1 exhibits strong inhibition against DPP4, but has lower activity inhibition against other DPP family members (DPP2, DPP8, and DPP9). Hence the compound of the present invention can not only effectively inhibit DPP4 from exhibiting medicinal activity, but also lower the activity inhibition against other members of the DPP family, reduce toxic side effect, and have better medicinal safety.
Synthesis and electrocatalytic water oxidation by electrode-bound helical peptide chromophore-catalyst assemblies
Ryan, Derek M.,Coggins, Michael K.,Concepcion, Javier J.,Ashford, Dennis L.,Fang, Zhen,Alibabaei, Leila,Ma, Da,Meyer, Thomas J.,Waters, Marcey L.
, p. 8120 - 8128 (2014/08/18)
Artificial photosynthesis based on dye-sensitized photoelectrosynthesis cells requires the assembly of a chromophore and catalyst in close proximity on the surface of a transparent, high band gap oxide semiconductor for integrated light absorption and catalysis. While there are a number of approaches to assemble mixtures of chromophores and catalysts on a surface for use in artificial photosynthesis based on dye-sensitized photoelectrosynthesis cells, the synthesis of discrete surface-bound chromophore-catalyst conjugates is a challenging task with few examples to date. Herein, a versatile synthetic approach and electrochemical characterization of a series of oligoproline-based light-harvesting chromophore-water-oxidation catalyst assemblies is described. This approach combines solid-phase peptide synthesis for systematic variation of the backbone, copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) as an orthogonal approach to install the chromophore, and assembly of the water-oxidation catalyst in the final step. Importantly, the catalyst was found to be incompatible with the conditions both for amide bond formation and for the CuAAC reaction. The modular nature of the synthesis with late-stage assembly of the catalyst allows for systematic variation in the spatial arrangement of light-harvesting chromophore and water-oxidation catalyst and the role of intrastrand distance on chromophore-catalyst assembly properties. Controlled potential electrolysis experiments verified that the surface-bound assemblies function as water-oxidation electrocatalysts, and electrochemical kinetics data demonstrate that the assemblies exhibit greater than 10-fold rate enhancements compared to the homogeneous catalyst alone.
MACROCYCLIC COMPOUNDS FOR INHIBITION OF INHIBITORS OF APOPTOSIS
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, (2013/05/23)
The invention relates generally to macrocyclic compounds and their therapeutic use. More particularly, the invention relates to macrocyclic compounds that modulate the activity of inhibitors of apoptosis (IAPs) and/or are useful in the treatment of medical conditions, such as cancer.
Remarkable structure effects on chiroptical properties of polyisocyanides carrying proline pendants
Xu, Anqiu,Hu, Guixia,Hu, Yulong,Zhang, Xiuqiang,Liu, Kun,Kuang, Guichao,Zhang, Afang
, p. 2003 - 2014 (2013/09/23)
Chiral polymers with simple chemical structures and high helical conformation stabilities are important for their applications as chiral supports and asymmetrical catalysts. We report herein the synthesis of a series of aliphatic polyisocyanides carrying proline pendants of different chiralities, and an investigation of the effects of the chemical structures of these pendants on the chiroptical properties of the polymers. The configuration of the chiral center at the 4-position of the proline pendants was changed from S to R to check its effect on the handedness of the helical conformation. To examine the effects of steric hindrance on the stabilities of the helical conformation for these aliphatic representatives, proline pendants with various substituents at both the carboxyl and amine terminals were designed. To further examine the steric effects of the proline pendants, aromatic counterparts were also prepared. In the latter case, the effects of hydrogen bonds between pendant units on the enhancement and stabilities of the helical conformation were investigated by switching from the ester to an amide linkage. The Cotton effects and signal intensities of both aliphatic and aromatic polyisocyanides from circular dichroism spectroscopy were compared based on the bulkiness of the pendant groups, solvent polarities, and solution temperatures. It was found that highly stable helical conformations of polyisocyanides could be imposed by small bulky monoproline pendants. Twisted sisters: Polyisocyanides with various proline-based pendant groups were synthesized and their chiroptical properties investigated. These chiral polymers show unprecedented stable helical conformations in different solvents at various temperatures, even in the absence of strong hydrogen-bonding interactions between the pendant groups (see picture). Copyright
Functionalizable oligoprolines as molecular scaffolds
Nagel, Yvonne A.,Kuemin, Michael,Wennemers, Helma
, p. 264 - 267 (2011/12/21)
Azidoproline (Azp) containing oligoprolines are conformationally well-defined, helical molecular scaffolds that allow for facile functionalization. Within this article we describe the synthesis of Azp-containing oligoprolines and different strategies to introduce functional moieties. In addition, the influence of factors such as substituents at the γ-position of proline as well as functional groups at the termini on the conformational stability of the molecular scaffolds are briefly presented. Schweizerische Chemische Gesellschaft.
Solid-phase synthesis of an apoptosis-inducing tetrapeptide mimicking the Smac protein
Le Quement, Sebastian T.,Ishoey, Mette,Petersen, Mette T.,Simonsen, Pernille M.,Holck, Nanna S.,Nielsen, Thomas E.
, p. 7049 - 7053 (2012/01/13)
An approach for the solid-phase synthesis of apoptosis-inducing Smac peptidomimetics is presented. Using a Rink linker strategy, tetrapeptides mimicking the N-4-terminal residue of the Smac protein [(N-Me)AVPF sequence] were synthesized on PEGA resin in excellent purities and yields. Following two synthetic routes, a known tetrapeptide, incorporating a substituted proline, previously shown to exhibit excellent biological activity in vitro as well as low toxicity, was synthesized effectively on a solid support.
Solid-phase synthesis of smac peptidomimetics incorporating triazoloprolines and biarylalanines
Le Quement, Sebastian T.,Ishoey, Mette,Petersen, Mette T.,Thastrup, Jacob,Hagel, Grith,Nielsen, Thomas E.
, p. 667 - 675 (2012/03/22)
Apoptotic induction mechanisms are of crucial importance for the general homeostasis of multicellular organisms. In cancer the apoptotic pathways are downregulated, which, at least partly, is due to an abundance of inhibitors of apoptosis proteins (IAPs) that block the apoptotic cascade by deactivating proteolytic caspases. The Smac protein has an antagonistic effect on IAPs, thus providing structural clues for the synthesis of new pro-apoptotic compounds. Herein, we report a solid-phase approach for the synthesis of Smac-derived tetrapeptide libraries. On the basis of a common (N-Me)AVPF sequence, peptides incorporating triazoloprolines and biarylalanines were synthesized by means of Cu(I)-catalyzed azide-alkyne cycloaddition and Pd-catalyzed Suzuki cross-coupling reactions. Solid-phase procedures were optimized to high efficiency, thus accessing all products in excellent crude purities and yields (both typically above 90%). The peptides were subjected to biological evaluation in a live/dead cellular assay which revealed that structural decorations on the AVPF sequence indeed are highly important for cytotoxicity toward HeLa cells.
Importance of ring puckering versus interstrand hydrogen bonds for the conformational stability of collagen
Erdmann, Roman S.,Wennemers, Helma
supporting information; experimental part, p. 6835 - 6838 (2011/09/19)
Mismatch is fine: Proline derivatives with a ring pucker mismatching that of natural collagen but with favorable torsional angles along the peptide chain are readily tolerated within the collagen triple helix (see picture). In contrast, a competition between intramolecular and interstrand H bonds destabilizes the collagen triple helix. Copyright
