74844-91-0Relevant articles and documents
Construction of Challenging Proline-Proline Junctions via Diselenide-Selenoester Ligation Chemistry
Sayers, Jessica,Karpati, Phillip M. T.,Mitchell, Nicholas J.,Goldys, Anna M.,Kwong, Stephen M.,Firth, Neville,Chan, Bun,Payne, Richard J.
, p. 13327 - 13334 (2018)
Polyproline sequences are highly abundant in prokaryotic and eukaryotic proteins, where they serve as key components of secondary structure. To date, construction of the proline-proline motif has not been possible owing to steric congestion at the ligatio
Synthesis of Ribo-Azanucleosides by Anodic Oxidation: Reactivity Control of Intermediate for Efficient Access to Pharmacophores
Okamoto, Kazuhiro,Shoji, Takao,Tsutsui, Mizuki,Shida, Naoki,Chiba, Kazuhiro
, p. 17902 - 17905 (2018)
Azanucleosides, the sugar-modified nucleoside analogues, have various biological activities, while their efficient synthetic strategy is still under development. Herein, a novel method for the synthesis of pharmaceutically relevant azanucleosides, β-anomers of ribo-azanucleosides, by means of site-specific anodic C?H activation by using a nitroalkane–lithium perchlorate medium is reported. A mechanistic study of the electrochemical reaction and the armed/disarmed concept from traditional glycochemistry revealed that the 2′-substituent has a significant effect on the reactivity of prolinol derivative, and suitable carboxylic acid additives can control the reactivity of the intermediate species, an iminium cation equivalent. Finally, this method was demonstrated to be applicable for the synthesis of β-anomers of ribo-azanucleosides with all four nucleobases in a stereoselective manner.
C3′-endo-puckered pyrrolidine containing PNA has favorable geometry for RNA binding: Novel ethano locked PNA (ethano-PNA)
Banerjee, Anjan,Kumar, Vaijayanti A.
, p. 4092 - 4101 (2013)
A novel peptide nucleic acid (PNA) analogue is designed with a constraint in the aminoethyl segment of the aegPNA backbone so that the dihedral angle β is restricted within 60-80, compatible to form PNA:RNA duplexes. The designed monomer is further functionalized with positively charged amino-/guanidino-groups. The appropriately protected monomers were synthesized and incorporated into aegPNA oligomers at predetermined positions and their binding abilities with cDNA and RNA were investigated. A single incorporation of the modified PNA monomer into a 12-mer PNA sequence resulted in stronger binding with complementary RNA over cDNA. No significant changes in the CD signatures of the derived duplexes of modified PNA with complementary RNA were observed.
A Highly Stereoselective and Scalable Synthesis of l -allo-Enduracididine
Craig, William,Chen, Janet,Richardson, David,Thorpe, Rondel,Yuan, Yu
, p. 4620 - 4623 (2015)
A highly stereoselective and scalable synthesis of l-allo-enduracididine from hydroxyproline derivative is described. Pyrrolidine oxidation and reductive ring opening are the key steps in the synthesis. Compared to previously reported approaches, the curr
Design and synthesis of fluorinated peptides for analysis of fluorous effects on the interconversion of polyproline helices
Li, Meng-Che,Liu, Ying-Jie,Hsu, Kuang-Cheng,Lin, Tse-Hsueh,Lin, Chih-Wei,Horng, Jia-Cherng,Wang, Sheng-Kai
, (2021/11/30)
The unique interaction between fluorine atoms has been exploited to alter protein structures and to develop synthetic and analytical applications. To expand such fluorous interaction for novel applications, polyproline peptides represent an excellent molecular nanoscaffold for controlling the presentation of perfluoroalkyl groups on their unique secondary structure. We develop approaches to synthesis fluorinated peptides to systematically investigate how the number, location and types of the fluorous groups on polyproline affect the conformation by monitoring the transition between the two major polyproline structures PPI and PPII. This work provides valuable information on how fluorous interaction affects the peptide structure and also benefits the design of functional fluorous molecules.
Altering the sex pheromone cyclo(L-pro-l-pro) of the diatom seminavis robusta towards a chemical probe
Bonneure, Eli,De Baets, Amber,De Decker, Sam,Van den Berge, Koen,Clement, Lieven,Vyverman, Wim,Mangelinckx, Sven
, p. 1 - 14 (2021/01/26)
As a major group of algae, diatoms are responsible for a substantial part of the primary production on the planet. Pennate diatoms have a predominantly benthic lifestyle and are the most species-rich diatom group, with members of the raphid clades being motile and generally having heterothallic sexual reproduction. It was recently shown that the model species Seminavis robusta uses multiple sexual cues during mating, including cyclo(L-Pro-L-Pro) as an attraction pheromone. Elaboration of the pheromone-detection system is a key aspect in elucidating pennate diatom life-cycle regulation that could yield novel fundamental insights into diatom speciation. This study reports the synthesis and bio-evaluation of seven novel pheromone analogs containing small structural alterations to the cyclo(L-Pro-L-Pro) pheromone. Toxicity, attraction, and interference assays were applied to assess their potential activity as a pheromone. Most of our analogs show a moderate-to-good bioactivity and low-to-no phytotoxicity. The pheromone activity of azide-and diazirine-containing analogs was unaffected and induced a similar mating behavior as the natural pheromone. These results demonstrate that the introduction of confined structural modifications can be used to develop a chemical probe based on the diazirine-and/or azide-containing analogs to study the pheromone-detection system of S. robusta.
Synthesis process of N-BOC-cis-4-hydroxyproline methyl ester
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Paragraph 0021-0023, (2021/01/20)
The invention discloses a synthesis process of N-BOC-cis-4-hydroxyproline methyl ester. The synthesis process comprises the following steps: (1) adding raw materials including dichloromethane, 4-hydroxy-L-proline and DMAP into a 2 L reaction flask, stirring, slowly dropwise adding BOC anhydride into the reaction liquid, after dropwise adding, sampling, carrying out TLC, completely reacting the rawmaterials, adding water into the reaction liquid after treatment, stirring at a temperature of 20-30 DEG C, separating the liquid, drying an organic phase by using anhydrous sodium sulfate, and concentrating under reduced pressure to obtain a white solid product; and (2) taking the obtained product, adding tetrahydrofuran and DCC into a 5 L reaction flask, stirring at 20-30 DEG C to react for 1 hour, dropwise adding methanol into the reaction solution, keeping the temperature after dropwise adding, sampling, carrying out TLC until the reaction is complete, filtering the reaction solution, collecting the filtrate, concentrating under reduced pressure until no liquid flows out to obtain a white solid crude product, heating, collecting the filtrate, collecting a filter cake, and drying the filter cake to obtain a white solid. According to the invention, the product is prepared with high quality and high yield.
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.
Design, Synthesis, and Biochemical Evaluation of Alpha-Amanitin Derivatives Containing Analogs of the trans-Hydroxyproline Residue for Potential Use in Antibody-Drug Conjugates
Braun, Alexandra,Gallo, Francesca,Hambira, Chido M.,Hechler, Torsten,Kato, Brandon,Müller, Christoph,Matinkhoo, Kaveh,Pahl, Andreas,Perrin, David M.,Wei, Charlie,Wong, Antonio A. W. L.
, p. 10282 - 10292 (2021/06/25)
Alpha-amanitin, an extremely toxic bicyclic octapeptide extracted from the death-cap mushroom, Amanita phalloides, is a highly selective allosteric inhibitor of RNA polymerase II. Following on growing interest in using this toxin as a payload in antibody-drug conjugates, herein we report the synthesis and biochemical evaluation of several new derivatives of this toxin to probe the role of the trans-hydroxyproline (Hyp), which is known to be critical for toxicity. This structure activity relationship (SAR) study represents the first of its kind to use various Hyp-analogs to alter the conformational and H-bonding properties of Hyp in amanitin.
Synthesis and evaluation of “Ama-Flash”, a photocaged amatoxin prodrug for light-activated RNA Pol II inhibition and cell death
Matinkhoo, Kaveh,Pryyma, Alla,Wong, Antonio A. W. L.,Perrin, David M.
supporting information, p. 9558 - 9561 (2021/09/28)
Amanitin is used extensively as a research tool to inhibit RNA Pol II thereby implicating its role in mRNA transcription. Recently, amanitin has gained traction as a toxic payload for targeted therapy. Here we report the first-ever photocaged amanitin analog, that is non-toxic and can be pre-loaded into cells. Light provides a means to inhibit RNA Pol II and provoke cell death on-demand.
