- Preparation and biological evaluation of soluble tetrapeptide epoxyketone proteasome inhibitors
-
A series of novel tetrapeptidyl epoxyketone inhibitors of 20S proteasome was designed and synthesized. To fully understand the SAR, various groups at R1, R2, R3, R4 and R5 positions, including aromatic and aliphatic substituents were designed, synthesized and biologically assayed. Based on the enzymatic results, seven compounds were selected to evaluate their cellular activities and soluble compound 36 showed strong potency against human multiple myeloma (MM) cell lines. Microsomal stability results indicated that compound 36 was more stable in mice, rat and human microsomes than marketed carfilzomib. The in vivo activities of this compound were evaluated with the xenograft mice models of MM cell lines ARH77 and RPMI-8226 with luciferase expression and the T/C value of the two models were 49.5% and 37.6%, respectively. To evaluate the potential cardiovascular toxicity, inhibition of hERG ion channel in HEK293 cells by compound 36 and carfilzomib was carried out. The results indicated that 36 had no binding affinity for the hERG ion channel while carfilzomib could bind it with IC50 of 92.1 μM.
- Lei, Meng,Zhang, Haoyang,Miao, Hang,Du, Xiao,Zhou, Hui,Wang, Jia,Wang, Xueyuan,Feng, Huayun,Shi, Jingmiao,Liu, Zhaogang,Shen, Jian,Zhu, Yongqiang
-
p. 4151 - 4162
(2019/08/07)
-
- The role of N-terminal heterocycles in hydrogen bonding to α-chymotrypsin
-
A series of dipeptide aldehydes containing different N-terminal heterocycles was prepared and assayed in vitro against α-chymotrypsin to ascertain the importance of the heterocycle in maintaining a β-strand geometry while also providing a hydrogen bond do
- Schumann, Nicholas C.,Bruning, John,Marshall, Andrew C.,Abell, Andrew D.
-
supporting information
p. 396 - 399
(2019/01/04)
-
- Pd-Catalyzed Site-Selective C(sp2)-H Olefination and Alkynylation of Phenylalanine Residues in Peptides
-
Pd-catalyzed site-selective C(sp2)-H olefination and alkynylation of phenylalanine residues in peptides are described. The amino acids within the peptides are used as native bidentate directing groups to facilitate C-H functionalization. This p
- Zheng, Yong,Song, Weibin
-
supporting information
(2019/05/08)
-
- Pd-catalyzed intramolecular C(sp2)-H amination of phenylalanine moieties in dipeptides: Synthesis of indoline-2-carboxylate-containing dipeptides
-
A palladium-catalyzed intramolecular C(sp2)-H amination of phenylalanine moieties in dipeptides is described. By this protocol, a series of indoline-2-carboxylate-containing dipeptides were synthesized from dipeptides. The N-protected amino aci
- Zheng, Yong,Song, Weibin,Zhu, Yefu,Wei, Bole,Xuan, Lijiang
-
supporting information
p. 2402 - 2405
(2018/04/12)
-
- Target Validation and Identification of Novel Boronate Inhibitors of the Plasmodium falciparum Proteasome
-
The Plasmodium proteasome represents a potential antimalarial drug target for compounds with activity against multiple life cycle stages. We screened a library of human proteasome inhibitors (peptidyl boronic acids) and compared activities against purified P. falciparum and human 20S proteasomes. We chose four hits that potently inhibit parasite growth and show a range of selectivities for inhibition of the growth of P. falciparum compared with human cell lines. P. falciparum was selected for resistance in vitro to the clinically used proteasome inhibitor, bortezomib, and whole genome sequencing was applied to identify mutations in the proteasome β5 subunit. Active site profiling revealed inhibitor features that enable retention of potent activity against the bortezomib-resistant line. Substrate profiling reveals P. falciparum 20S proteasome active site preferences that will inform attempts to design more selective inhibitors. This work provides a starting point for the identification of antimalarial drug leads that selectively target the P. falciparum proteasome.
- Xie, Stanley C.,Gillett, David L.,Spillman, Natalie J.,Tsu, Christopher,Luth, Madeline R.,Ottilie, Sabine,Duffy, Sandra,Gould, Alexandra E.,Hales, Paul,Seager, Benjamin A.,Charron, Carlie L.,Bruzzese, Frank,Yang, Xiaofeng,Zhao, Xiansi,Huang, Shih-Chung,Hutton, Craig A.,Burrows, Jeremy N.,Winzeler, Elizabeth A.,Avery, Vicky M.,Dick, Lawrence R.,Tilley, Leann
-
supporting information
p. 10053 - 10066
(2018/11/23)
-
- A dipeptide-based superhydrogel: Removal of toxic dyes and heavy metal ions from waste water
-
A short peptide-based molecule has been found to form a strong hydrogel at phosphate buffer solution of pH 7.46. The hydrogel has been characterized thoroughly using various techniques including field emission scanning electron microscopy (FE-SEM), wide angle powder X-ray diffraction (PXRD), and rheological analysis. It has been observed from FE-SEM images that entangled nanofiber network is responsible for gelation. Rheological investigation demonstrates that the self-assembly of this synthetic dipeptide results in the formation of mechanically strong hydrogel with storage modulus (G′) around 104 Pa. This gel has been used for removing both cationic and anionic toxic organic dyes (Brilliant Blue, Congo red, Malachite Green, Rhodamine B) and metal ions (Co2+ and Ni2+) from waste water. Moreover, only a small amount of the gelator is required (less than 1 mg/mL) for preparation of this superhydrogel and even this hydrogel can be reused three times for dye/metal ion absorption. This signifies the importance of the hydrogel towards waste water management.
- Nandi, Nibedita,Baral, Abhishek,Basu, Kingshuk,Roy, Subhasish,Banerjee, Arindam
-
-
- METHODS OF MAKING CARFILZOMIB AND INTERMEDIATES THEREOF
-
Racemization-free methods are disclosed for the synthesis of carfilzomib. Novel intermediates and methods of making carfilzomib employing fragment condensation using the novel intermediates are disclosed. Amorphous carfilzomib and methods of making same are disclosed.
- -
-
-
- PROCESS FOR THE PREPARATION OF (2S)-N-((S)-1-((S)-4-METHYL-1-((R)-2-METHYL OXIRAN-2-YL)-1-OXOPENTAN-2-YLCARBAMOYL)-2-PHENYLETHYL)-2-((S)-2-(2-MORPHOLINO ACETAMIDO)-4-PHENYLBUTANAMIDO)-4-METHYLPENTANAMIDE
-
The present invention relates to process for the preparation of (2S)-N-((S)-l -((S)-4-methyl-1 -((R)-2-methyloxiran-2-yl)-1-oxopentan-2-ylcarbamoyl)-2-phenylethyl)-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)-4 -methylpentanamide represented by the following structural formula-1.
- -
-
-
- Synthesis of Natural and Unnatural Cyclooligomeric Depsipeptides Enabled by Flow Chemistry
-
Flow chemistry has been successfully integrated into the synthesis of a series of cyclooligomeric depsipeptides of three different ring sizes including the natural products beauvericin (1 a), bassianolide (2 b) and enniatin C (1 b). A reliable flow chemistry protocol was established for the coupling and macrocyclisation to form challenging N-methylated amides. This flexible approach has allowed the rapid synthesis of both natural and unnatural depsipeptides in high yields, enabling further exploration of their promising biological activity. Harnessing technology: Flow chemistry has been successfully integrated into the synthesis of a series of cyclooligomeric depsipeptides of three different ring sizes including the natural products beauvericin (1 a), bassianolide (2 b) and enniatin C (1 b), resulting in increased overall yields, while decreasing the effort required for the researcher.
- Lücke, Daniel,Dalton, Toryn,Ley, Steven V.,Wilson, Zoe E.
-
p. 4206 - 4217
(2016/03/16)
-
- Towards the first total synthesis and anticancer screening of polycarponin C: A cyclic octapeptide
-
The present study describes designing, synthesis and anticancer screening of a proline rich cyclic octapeptide polycarponin C, by solution phase synthesis. The synthesis was carried out by coupling a tetrapeptide Boc-Pro-Thr-Leu-Pro-OH with another tetrap
- Shinde, Nirmala V.,Dhake, Avinash S.,Havalavalaval, Kishan P.
-
p. 515 - 521
(2016/05/09)
-
- Iodine-Mediated Oxidative Coupling of Hydroxamic Acids with Amines towards a New Peptide-Bond Formation
-
An efficient and straightforward approach for the coupling of Nα-protected hydroxamic acids with an amino component in the presence of iodine is delineated. The reaction is mediated by the formation of unstable but reactive acyl nitroso intermediates. The peptide hydroxamic acids were found to be useful substrates in coupling reactions.
- Krishnamurthy, Muniyappa,Vishwanatha,Panguluri, Nageswara Rao,Panduranga,Sureshbabu, Vommina V.
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supporting information
p. 2565 - 2569
(2015/11/16)
-
- Additivity or cooperativity: Which model can predict the influence of simultaneous incorporation of two or more functionalities in a ligand molecule?
-
Predicting how binding affinity responds to ligand structural modifications in structure-activity relationship studies (SAR) is a major challenge in medicinal chemistry. This is particularly true when two or more of these modifications are carried out simultaneously. In this study, we present binding affinity data from several series of thermolysin inhibitors in which simultaneous structural modifications were investigated to determine whether they are cooperative or additive. Data revealed that, while additivity is at work in some cases, cooperativity is more commonly demonstrated. Cooperativity and additivity were then correlated with ligand descriptors, such as the spacing and the topological features of the modified groups, in a manner that may provide guidance as to when each model should be utilized. Cooperativity was particularly associated with contiguous groups and small unbranched hydrophobic side chain. Additivity, on the other hand, was associated with moderately distant hydrophobic group combinations and side chain branching. Such correlations can improve the predictability of SAR studies and can provide a starting point for additional investigations that may lead to further significant enhancements in the current scoring functions.
- Nasief, Nader N.,Hangauer, David
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p. 897 - 915
(2015/05/27)
-
- Room temperature N-arylation of amino acids and peptides using copper(i) and β-diketone
-
A mild and efficient method for the N-arylation of zwitterionic amino acids, amino acid esters and peptides is described. The procedure provides the first room temperature synthesis of N-arylated amino acids and peptides using CuI as a catalyst, diketone as a ligand, and aryl iodides as coupling partners. The method is equally applicable for using relatively inexpensive aryl bromides as coupling partners at 80 °C. Using this procedure, electronically and sterically diverse aryl halides, containing reactive functional groups were efficiently coupled in good to excellent yields.
- Sharma, Krishna K.,Sharma, Swagat,Kudwal, Anurag,Jain, Rahul
-
supporting information
p. 4637 - 4641
(2015/04/27)
-
- CRYSTALLINE PEPTIDE EPOXY KETONE PROTEASE INHIBITORS AND THE SYNTHESIS OF AMINO ACID KETO-EPOXIDES
-
The invention relates to crystalline peptide keto epoxide compounds, methods of their preparation, and related pharmaceutical compositions. This invention also relates to methods for the preparation of amino acid keto-epoxides. Specifically, allylic ketones are stereoselectively converted to the desired keto epoxides.
- -
-
Paragraph 0447-0450
(2016/10/27)
-
- PEPTIDE EPOXYKETONE COMPOUNDS
-
The present disclosure relates to novel compounds and pharmaceutical compositions thereof which are useful as inhibitors of proteasomes. The compounds provided herein are capable of inhibiting all three of CT-L, T-L, and PGPH activities of proteasomes, and are useful in treating various conditions or diseases associated with proteasomes.
- -
-
Paragraph 00267; 00268
(2014/02/16)
-
- Influence of neighboring groups on the thermodynamics of hydrophobic binding: An added complex facet to the hydrophobic effect
-
The thermodynamic consequences of systematic modifications in a ligand side chain that binds in a shallow hydrophobic pocket, in the presence and absence of a neighboring ligand carboxylate group, were evaluated using isothermal titration calorimetry (ITC
- Nasief, Nader N.,Hangauer, David
-
supporting information
p. 2315 - 2333
(2014/04/17)
-
- Redox-triggered changes in the self-assembly of a ferrocene-peptide conjugate
-
Ultrasonication of a ferrocene conjugate of a short amyloid peptide (Aβ18-20) in toluene causes formation of an organogel, which undergoes dramatic structural changes upon oxidation from a nanofibrillar network to spherical micelles. This morphological change is redox-controlled and reversible. the Partner Organisations 2014.
- Adhikari, Bimalendu,Kraatz, Heinz-Bernhard
-
supporting information
p. 5551 - 5553
(2014/05/20)
-
- Dissecting the hydrophobic effect on the molecular level: The role of water, enthalpy, and entropy in ligand binding to thermolysin
-
The hydrophobic effect is associated with the successive replacement of water molecules in the binding site of a protein by hydrophobic groups of the ligand. Although the hydrophobic effect is assumed to be entropy-driven, large changes in enthalpy and entropy are observed with the model system thermolysin. Structural changes in the binding features of the water molecules ultimately determine the thermodynamics of the hydrophobic effect. Copyright
- Biela, Adam,Nasief, Nader N.,Betz, Michael,Heine, Andreas,Hangauer, David,Klebe, Gerhard
-
supporting information
p. 1822 - 1828
(2013/04/23)
-
- Synthesis of a novel series of L-isoserine derivatives as aminopeptidase N inhibitors
-
A series of novel L-isoserine derivatives were synthesised and evaluated for their ability to inhibit aminopeptidase N (APN)/CD13. In our preliminary biological results, some of these compounds possessed a potent inhibitory activity against the APN. Within this series, compound 14b not only showed similar enzyme inhibition (IC50 of 12.2μM) compared with the positive control bestatin (half maximal inhibitory concentration (IC 50) of 7.3μM), but also had a potent antiproliferative activity against human cancer cell lines cells.
- Yang, Kanghui,Fen, Jinghong,Fang, Hao,Zhang, Lei,Gong, Jianzhi,Xu, Wenfang
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p. 302 - 310
(2012/07/02)
-
- An efficient entry to highly substituted chiral 2-oxopiperazines from α-amino acids via iodocyclization
-
A short and stereoselective route for the synthesis of 2-oxopiperazines is presented starting from different naturally abundant α-amino acids. The key synthetic steps involved amide coupling, Wittig reaction, HWE olefination, aza-Michael reaction, iodocyc
- Jana, Amit Kumar,Das, Sanjit Kumar,Panda, Gautam
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p. 10114 - 10121,8
(2020/09/02)
-
- Synthesis of sansalvamide A peptidomimetics: Triazole, oxazole, thiazole, and pseudoproline containing compounds
-
Peptidomimetic-based macrocycles typically have improved pharmacokinetic properties over those observed with peptide analogs. Described are the syntheses of 13 peptidomimetic derivatives that are based on active sansalvamide A structures, where these analogs incorporate heterocycles (triazoles, oxazoles, thiazoles, or pseudoprolines) along the macrocyclic backbone. The syntheses of these derivatives employ several approaches that can be applied to convert a macrocyclic peptide into its peptidomimetic counterpart. These approaches include peptide modifications to generate the alkyne and azide for click chemistry, a serine conversion into an oxazole, a Hantzsch reaction to generate the thiazole, and protected threonine to generate the pseudoproline derivatives. Furthermore, we show that two different peptidomimetic moieties, triazoles, and thiazoles, can be incorporated into the macrocyclic backbone without reducing cytotoxicity: triazole and thiazole.
- Davis, Melinda R.,Singh, Erinprit K.,Wahyudi, Hendra,Alexander, Leslie D.,Kunicki, Joseph B.,Nazarova, Lidia A.,Fairweather, Kelly A.,Giltrap, Andrew M.,Jolliffe, Katrina A.,McAlpine, Shelli R.
-
experimental part
p. 1029 - 1051
(2012/02/15)
-
- Cyclic dipeptides exhibit potency for scavenging radicals
-
Twenty kinds of cyclic dipeptides containing l-leucine were synthesized, and their antioxidant activity against .OH and O2·- was investigated. Compounds possessing polar amino acid residues, such as Asp, Cys, Glu, Lys, Pro, Ser, and Trp, exhibited higher antioxidant activity against .OH than vitamin E. However, only cyclo(l-Cys-l-Leu) scavenged O2·-.
- Furukawa, Tadashi,Akutagawa, Takashi,Funatani, Hitomi,Uchida, Toshikazu,Hotta, Yoshihiro,Niwa, Masatake,Takaya, Yoshiaki
-
experimental part
p. 2002 - 2009
(2012/05/04)
-
- 17α-ethynylestradiol peptide labeling by 'click' chemistry
-
A synthesis of 17α-ethynylestradiol-labeled native peptides is reported. The peptide moiety is tethered to the steroid hormone by a 1,2,3-triazole bridge formed by a CuAAC reaction in which the azido group of the peptide combines with the terminal acetylenic moiety of ethynylestradiol to link the two bioactive molecules. Thus bioconjugates containing the hormone moiety at three positions within the peptide molecule could be useful targets for hormono-enzyme interaction studies. Georg Thieme Verlag Stuttgart ? New York.
- Bol'Shakov, Oleg I.,Lebedyeva, Iryna O.,Katritzky, Alan R.
-
p. 2926 - 2932
(2012/10/29)
-
- Organometallic peptide NHC complexes of CpRh(III) and arene Ru(II) moieties from l-thiazolylalanine
-
The 3-ethyl thiazolium peptide salts Boc-Thia-Leu-OMe and Boc-Thia-Leu-Phe-OMe based on the unnatural amino acid thiazolylalanine (Thia) have been prepared. After deprotonation, they reacted rapidly via the silver carbene transfer reaction with [RhCpCl2]2 and [Ru(p-cymene)Cl2]2 to yield the corresponding thiazole-based carbene complexes 7-10 in acceptable yield. All new compounds were characterized by multinuclear NMR spectroscopy, mass spectrometry, and elemental analysis. These complexes constitute the first examples of thiazolylalanine-2-ylidene metal bioconjugates.
- Lemke, Jessica,Metzler-Nolte, Nils
-
experimental part
p. 1018 - 1022
(2011/04/25)
-
- Salts responsive nanovesicles through π-Stacking induced self-assembly of backbone modified tripeptides
-
A set of backbone modified peptides of general formula Boc-Xx-m-ABA-Yy-OMe where m-ABA is meta-aminobenzoic acid and Xx and Yy are natural amino acids such as Phe, Gly, Pro, Leu, Ile, Tyr and Trp etc., are found to self-assemble into soft nanovesicular st
- Koley, Pradyot,Drew, Michael G.B.,Pramanik, Animesh
-
experimental part
p. 6747 - 6756
(2012/05/20)
-
- Design and synthesis of Hsp90 inhibitors: Exploring the SAR of Sansalvamide A derivatives
-
Utilizing the structure-activity relationship we have developed during the synthesis of the first two generations and mechanism of action studies that point to the interaction of these molecules with the key oncogenic protein Hsp90, we report here the design of 32 new Sansalvamide A derivatives and their synthesis. Our new structures, designed from previously reported potent compounds, were tested for cytotoxicity on the HCT116 colon cancer cell line, and their binding to the biological target was analyzed using computational studies involving blind docking of derivatives using Autodock. Further, we show new evidence that our molecules bind directly to Hsp90 and modulate Hsp90's binding with client proteins. Finally, we demonstrate that we have integrated good ADME properties into a new derivative.
- Sellers, Robert P.,Alexander, Leslie D.,Johnson, Victoria A.,Lin, Chun-Chieh,Savage, Jeremiah,Corral, Ricardo,Moss, Jason,Slugocki, Tim S.,Singh, Erinprit K.,Davis, Melinda R.,Ravula, Suchitra,Spicer, Jamie E.,Oelrich, Jenna L.,Thornquist, Andrea,Pan, Chung-Mao,McAlpine, Shelli R.
-
experimental part
p. 6822 - 6856
(2010/10/18)
-
- A comprehensive study of Sansalvamide A derivatives: The structure-activity relationships of 78 derivatives in two pancreatic cancer cell lines
-
We report an extensive structure-activity relationship (SAR) of 78 compounds active against two pancreatic cancer cell lines. Our comprehensive evaluation of these compounds utilizes SAR that allow us to evaluate which features of potent compounds play a
- Pan, Po-Shen,Vasko, Robert C.,Lapera, Stephanie A.,Johnson, Victoria A.,Sellers, Robert P.,Lin, Chun-Chieh,Pan, Chung-Mao,Davis, Melinda R.,Ardi, Veronica C.,McAlpine, Shelli R.
-
experimental part
p. 5806 - 5825
(2009/12/24)
-
- Comprehensive study of sansalvamide A derivatives and their structure-activity relationships against drug-resistant colon cancer cell lines
-
We report an extensive structure-activity relationship (SAR) of 62 compounds active against two drug-resistant colon cancer cell lines. Our comprehensive evaluation of two generations of compounds utilizes SAR, NMR, and molecular modeling to evaluate the
- Otrubova, Katerina,Lushington, Gerald,Vander Velde, David,McGuire, Kathleen L.,McAlpine, Shelli R.
-
p. 530 - 544
(2008/09/18)
-
- Synthesis and cytotoxicity of a new class of potent decapeptide macrocycles
-
(Chemical Equation Presented) Described are the syntheses of five decapeptides that are C-2-symmetrical derivatives of the natural product pentapeptide sansalvamide A. Derivatives were made using a succinct convergent synthesis. These analogues share no s
- Davis, Melinda R.,Styers, Thomas J.,Rodriguez, Rodrigo A.,Pan, Po-Shen,Vasko, Robert C.,McAlpine, Shelli R.
-
p. 177 - 180
(2008/09/19)
-
- Synthesis and biological activity of peptide derivatives of iodoquinazolinones/nitroimidazoles
-
Two substituted quinazolinyl/imidazolyl-salicylic acids 5, 6 were synthesized by the reaction of 6-iodo-2-methylbenzoxazin-4-one/5-nitroimidazole with 5-aminosalicylic acid (5-ASA). Coupling of compounds 5 and 6 with different amino acid ester hydrochlorides, dipeptide and tripeptide methyl esters yielded novel quinazolino/imidazolopeptide derivatives 5a-f and 6a-g. The chemical structures of all newly synthesized compounds were confirmed by means of FT-IR, 1H- and 13C-NMR, MS and elemental analysis. Selected peptide ester derivatives were further hydrolyzed by using lithium hydroxide (LiOH) to afford the corresponding acid derivatives 5ba-da and 6ea-ga. All peptide derivatives were assayed for antimicrobial and anthelmintic activities against eight pathogenic microbes and three earthworm species. Among the tested compounds, 5e, 5d, 6e and their hydrolyzed analogs 5da and 6ea exhibited higher antimicrobial activity against Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans, and 5a, 6g and 6ga displayed better antifungal activity against the dermatophytes Trichophyton mentagrophytes and Microsporum audouinii. Moreover, 6f and its hydrolyzed derivative 6fa showed good anthelmintic activity against Megascoplex konkanensis, Pontoscotex corethruses and Eudrilus eugeniea at dose of 2 mg mL-1.
- Dahiya, Rajiv,Kumar, Anil,Yadav, Rakesh
-
p. 958 - 976
(2008/09/20)
-
- Synthesis of second-generation Sansalvamide A derivatives: Novel templates as potential antitumor agents
-
We report the synthesis of 34 second-generation Sansalvamide A derivatives. San A derivatives have unique anticancer properties and target multiple cancers, including colon, pancreatic, breast, prostate, and melanoma. As novel templates, the derivatives d
- Rodriguez, Rodrigo A.,Pan, Po-Shen,Pan, Chung-Mao,Ravula, Suchitra,Lapera, Stephanie,Singh, Erinprit K.,Styers, Thomas J.,Brown, Joseph D.,Cajica, Julia,Parry, Emily,Otrubova, Katerina,McAlpine, Shelli R.
-
p. 1980 - 2002
(2007/10/03)
-
- Immobilized triazine-type dehydrocondensing reagents for carboxamide formation: ROMP-Trz-Cl and ROMP(OH)-Trz-Cl
-
New triazine-type dehydrocondensing reagents, such as ROMP-Trz-Cl and ROMP(OH)-Trz-Cl, were synthesized by a ring opening metathesis polymerization (ROMP) method, and these showed higher loading than conventional polymer-supported condensing reagents. The
- Hioki, Kazuhito,Kameyama, Satomi,Tani, Shohei,Kunishima, Munetaka
-
p. 825 - 828
(2008/02/08)
-
- Development of chlorotriazine polymer dehydrocondensing reagents (Poly-Trzs)
-
Polymer-type dehydrocondensing reagents comprising of a triazine dehydrocondensing reagent, itself in a polymerized form (Poly-Trz-MMs'), have been developed by exploiting the chemical properties of cyanuric chloride that readily binds to alcohol or amines. A chlorotriazine polymer bearing two alkoxy substituents at the 4- and 6- positions (Poly-O-Trz-Cl) was prepared by alternating copolymerization between cyanuric chloride and tetra(ethylene glycol). Similarly, polymers bearing both alkoxy and amino substituents (Poly-N-Trz-Cl) were synthesized from tetra(ethylene glycol) bis(4,6-dichlorotriazin-2-yl) ether 6 and tris(2-aminoethyl)amine 7 and/or ethylenediamine 8. All the polymers were shown to be good reagents for dehydrocondensation of carboxylic acids and amines in the presence of NMM, compared to the corresponding monomeric dehydrocondensing reagent (DMT-MM). The advantages of the polymeric reagents are as follows: (1) both the reaction and isolation procedure of dehydrocondensation can be greatly simplified, (2) the dehydrocondensation can be conducted in protic solvents as well as in common organic solvents, (3) the reagents can be efficiently prepared at a low cost, and (4) these reagents are considered eco-friendly, generating a lower amount of waste compared to conventionally related reagents because of high loading of the dehydrocondensing activity (ca. 3 mequiv/g).
- Kunishima, Munetaka,Yamamoto, Kazuyoshi,Hioki, Kazuhito,Kondo, Tomohito,Hasegawa, Masumi,Tani, Shohei
-
p. 2604 - 2612
(2007/10/03)
-
- MACROCYCLIC PEPTIDES AND METHODS FOR MAKING AND USING THEM
-
The invention provides novel macrocyclic peptides and methods for their preparation. The invention also provides pharmaceutical compositions and methods to treat, prevent or ameliorate a cell proliferative disease or conditions, e.g., a cancer, in a subje
- -
-
Page/Page column 41-42
(2008/06/13)
-
- High-yielding macrocyclization conditions used in the synthesis of novel Sansalvamide A derivatives
-
Described are the syntheses of nine Sansalvamide A derivatives using new, high-yielding, in situ deprotection-cyclization conditions that are general for this series of macrocycles, 55% average for both steps. This is 10-fold greater than previously repor
- Styers, Thomas J.,Rodriguez, Rodrigo,Pan, Po-Shen,McAlpine, Shelli R.
-
p. 515 - 517
(2007/10/03)
-
- Synthesis of Sansalvamide A derivatives and their cytotoxicity in the MSS colon cancer cell line HT-29
-
We report the synthesis of thirty-six Sansalvamide A derivatives, and their biological activity against colon cancer HT-29 cell line, a microsatellite stable (MSS) colon cancer cell-line. The thirty-six compounds can be divided into three subsets, where t
- Styers, Thomas J.,Kekec, Ahmet,Rodriguez, Rodrigo,Brown, Joseph D.,Cajica, Julia,Pan, Po-Shen,Parry, Emily,Carroll, Chris L.,Medina, Irene,Corral, Ricardo,Lapera, Stephanie,Otrubova, Katerina,Pan, Chung-Mao,McGuire, Kathleen L.,McAlpine, Shelli R.
-
p. 5625 - 5631
(2007/10/03)
-
- Synthesis and cytotoxicity of novel Sansalvamide A derivatives
-
(Chemical Equation Presented) Described are the syntheses of 14 derivatives of the natural product Sansalvamide A, where two are more active against HCT 116 colon cancer cell lines than the natural product. These derivatives were synthesized using a combi
- Carroll, Chris L.,Johnston, Jennifer V. C.,Kekec, Ahmet,Brown, Joseph D.,Parry, Emily,Cajica, Julia,Medina, Irene,Cook, Kristina M.,Corral, Ricardo,Pan, Po-Shen,McAlpine, Shelli R.
-
p. 3481 - 3484
(2007/10/03)
-
- Compounds for enzyme inhibition
-
Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases. The activities of those Ntn having multiple activities can be differentially inhibited by the compounds described. For example, the chymotrypsin-like activity of the 20S proteasome may be selectively inhibited with the inventive compounds. The peptide-based compounds include at least three peptide units, an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation.
- -
-
Page/Page column 25-26
(2008/06/13)
-
- Approach to green chemistry of DMT-MM: Recovery and recycle of coproduct to chloromethane-free DMT-MM
-
A simple procedure for the isolation of 2-hydroxy-4,6-dimethoxy-1,3,5-triazine (HO-DMT), a coproduct arising from dehydrating condensation using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) has been established. HO-DMT can be recycled by treatment with POCl3 to give 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT), which is further converted to DMT-MM. Alternatively, reaction with triflic anhydride followed by addition of N-methylmorpholine gives DMT-MM triflate.
- Kunishima, Munetaka,Hioki, Kazuhito,Wada, Ayako,Kobayashi, Hiroko,Tani, Shohei
-
p. 3323 - 3326
(2007/10/03)
-
- METHOD FOR STORING QUATERNARY AMMONIUM SALT
-
A method of improving the stability of a quaternary ammonium salt and a method of efficiently preparing the quaternary ammonium salt having improved stability.
- -
-
-
- Stereoselective syntheses of 1H-imidazo[2,1-a]isoindole-2,5(3H,9bH)-diones
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1H-Imidazo[2,1-a]isoindole-2,5(3H,9bH)-diones 6a-i are synthesized in 67-96% yields with high stereoselectivities (de 88-99%, except 6e with a 58% de value) via intermolecular condensation of 2-formylbenzoic acid (5) and α-amino amides 4a-i in the presence of a catalytic amount of toluene-p-sulfonic acid. Intermediates 4 are obtained in two steps from easily available chiral N-Boc-α-amino acids 1.
- Katritzky,Xu,He,Steel
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p. 1767 - 1770
(2007/10/03)
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- Formation of carboxamides by direct condensation of carboxylic acids and amines in alcohols using a new alcohol- and water-soluble condensing agent: DMT-MM
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Selective formation of carboxamides in an alcohol or water by an exceptionally convenient one-step procedure in which a condensing agent is simply added to a mixture of acids and amines has been achieved successfully by using a new condensing agent, 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). Activation of carboxylic acids by DMT-MM in the presence of amines and subsequent aminolysis of the resulting acyloxytriazine in alcoholic solvents occurred selectively and led to the formation of carboxamides in excellent yields. The rate of aminolysis of the acyloxytriazine intermediate can be estimated to be about 2×104 times greater than that of methanolysis. The amide/ester selectivity observed using DMT-MM was much larger than that obtained with DCC or EDC. Condensation of polar substrates, such as amino acid esters and their hydrochlorides, glucosamine hydrochloride, sodium acetate and dicarboxylic acids, proceeded successfully in MeOH, water or aqueous MeOH in good yields. The present reaction is technically quite simple and easy to achieve. It proceeds by simple mixing of acids, amines and DMT-MM without any additives, and the MeOH is readily removable by a rotary evaporator after completion of the reaction.
- Kunishima, Munetaka,Kawachi, Chiho,Hioki, Kazuhito,Terao, Keiji,Tani, Shohei
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p. 1551 - 1558
(2007/10/03)
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- The importance of the methionine configuration in for-Met-Leu-Phe-OMe biological activities
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for-D-Met-L-Leu-L-Phe-OMe was synthesized in order to understand the importance of the methionine configuration on human neutrophil biological activity. Our results show that both chemotactic response and lysozyme release are lower than those of the parent fMLP-OMe, indicating that the specific receptor pocket possesses a well-located, restricted positive area that does not completely face the D-Met residue. The triggering of superoxide anion production does not seem to be sensitive to this variation of the configuration. (C) 2000 Academic Press.
- Spisani, Susanna,Cavicchioni, Giorgio
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- Differences arising in human neutrophil activation passing from N-formyl to N-acetyl-oligopeptides
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N-formyl- and N-acetyl-peptides were synthesized and compared in order to understand which features can best elicit biological responses. The behavior of N-formyl-peptides confirms the previously found sequential obligations in the residues, while acetyl-
- Spisani, Susanna,Cavicchioni, Giorgio
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p. 252 - 259
(2007/10/03)
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- Conformational aspects of human formylpeptide receptor antagonists
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The conformation of several Phe-D-Leu-Phe-D-Leu-Phe analogues was analyzed using infrared absorption and circular dichroism. Their effect on human neutrophils was verified by receptor binding and chemotaxis assays. The results demonstrate that the compounds examined prefer an ordered conformation (β-turn) in amphipatic environment, and that they are able to antagonize the neutrophil functions evoked by CHO-Met-Leu-Phe.
- Scatturin, Angelo,Vertuani, Gianni,Pecoraro, Rita,Dalpiaz, Alessandro,Boggian, Marisa,Ferretti, Maria Enrica,Spisani, Susanna
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p. 873 - 877
(2007/10/03)
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- Comparative lipase-catalyzed hydrolysis of ethylene glycol derived esters. The 2-methoxyethyl ester as a protective group in peptide and glycopeptide synthesis
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Comparison of the lipase-catalyzed cleavage of polar esters derived from ethylene glycol proved 2-methoxyethyl (ME) esters most favorable protecting groups for the carboxylic function of peptides and glycopeptides. They combine high substrate acceptance and iligh yields of hydrolysis with favorable physicochemical properties and advantageous solubility. The application of this polar ester as protecting group was extended to N-glycosylated amino acids and N-glycopeptides. The selective removal of ME esters by lipases was achieved under mild conditions (pH 7.0 and 37°C), leaving all other linkages including peptide bonds and other ester protecting groups unaffected.
- Gewehr, Markus,Kunz, Horst
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p. 1499 - 1510
(2007/10/03)
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- Destruxin analogues: Depsi peptidic bond replacement by amide bond
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In order to determine the importance of the depsi bond present in natural destruxins, we have investigated the replacement of this ester bond by an amide bond, leading to a new family of analogues. Synthesis of six specific members of this new class of compounds is reported. Since none of these cyclopeptides showed any biological activity, we undoubtedly proved that the depside group is a requisite for insecticide effect.
- Cavelier,Jacquier,Mercadier,Verducci
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p. 6173 - 6186
(2007/10/03)
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- Conformational effects in reversed-phase liquid chromatographic separation of diastereomers of cyclic dipeptides
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The capacity factors, k′, of 11 cyclic dipeptides (X-Y) including diastereomers have been determined on an RP-HPLC column in 30% and 50% methanol and 10%, 30%, and 50% acetonitrile solutions. These factors are roughly correlated with hydrophobic parameters, such as octanol-water partition coefficients estimated and k′ values for alcohols. For a pair of diastereomers of cyclic (L-X-L-Phe) and (L-X-D-Phe) derivatives k′LL is larger than k′LD and for cyclic (D-Ala-L-Trp) and (L-Ala-L-Trp) k′LL is smaller than k′DL, particularly in highly aqueous solutions. These elution orders can be well predicted by the holistic molecular surface area approach which takes into account the folded structures of cyclic dipeptides. The present results will be useful for prediction of the log k′ values of larger peptides and the hydrophobicity and related properties of peptides.
- Funasaki, Noriaki,Hada, Sakae,Neya, Saburo
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p. 1861 - 1867
(2007/10/02)
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