61058-41-1Relevant academic research and scientific papers
Rational Design of Small Peptides for Optimal Inhibition of Cyclooxygenase-2: Development of a Highly Effective Anti-Inflammatory Agent
Singh, Palwinder,Kaur, Sukhmeet,Kaur, Jagroop,Singh, Gurjit,Bhatti, Rajbir
, p. 3920 - 3934 (2016/05/24)
Among the small peptides 2-31, (H)Gly-Gly-Phe-Leu(OMe) (30) reduced prostaglandin production of COX-2 with an IC50 of 60 nM relative to 6000 nM for COX-1. The 5 mg kg-1 dose of compound 30 rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of compound 30 for targeting COX-2, iNOS, and VGSC was investigated by using substance P, l-arginine, and veratrine, respectively, as biomarkers. The interactions of 30 with COX-2 were supported by isothermal calorimetry experiments showing a Ka of 6.10 ± 1.10 × 104 M-1 and ΔG of -100.3 kJ mol-1 in comparison to a Ka 0.41 × 103 ± 0.09 M-1 and ΔG of -19.2 ± 0.06 kJ mol-1 for COX-1. Moreover, compound 30 did not show toxicity up to a 2000 mg kg-1 dose. Hence, we suggest peptide 30 as a highly potent and promising candidate for further development into an anti-inflammatory drug.
Total syntheses of arenamides A, B and C
Chandrasekhar, Srivari,Sathish, Kurapati,Reddy, Gangireddy Pavan Kumar,Mainkar, Prathama S.
, p. 348 - 355 (2014/04/03)
Total syntheses of the three arenamides A-C, NFκB inhibitors, are described for the first time. The key steps involved in the synthesis are a Crimmin's aldol, Wittig olefination and a macrolactamization reaction.
Total synthesis of arenamide A and its diastereomer
Chandrasekhar,Pavankumarreddy,Sathish
scheme or table, p. 6851 - 6854 (2010/05/03)
Arenamide A and its diastereomer have been synthesized in a convergent fashion. The key steps involved in this synthesis are Sharpless asymmetric epoxidation, C-C bond formation, and macrolactamization.
Use of polymer-bound 4-dialkylaminopyridines in peptide synthesis
Frontin, F. Cavelier,Guendouz, F.,Jacquier, R.,Verducci, J.
, p. 463 - 467 (2007/10/02)
This work describes the use of polymer-bound 4-dialkylaminopyridines as catalyst in peptide bond formation.In comparison with their soluble analogues, such as DMAP, these less basic compounds are less favorable to formation of oxazolone intermediate, and lead to peptide bond formation in good yields, and generally very low racemization. Key words: DMAP; polymer-bound dialkylaminopyridines; peptide synthesis; racemization.
KINETICS OF THE ALKALINE HYDROLYSIS OF SEVERAL N-BENZYLOXYCARBONYLDIPEPTIDE METHYL AND ETHYL ESTERS
Hoogwater, D. A.,Peereboom, M.
, p. 5325 - 5332 (2007/10/02)
The reaction rates of the alkaline hydrolysis of synthesized N-protected dipeptide methyl and ethyl esters were studied systematically.From the kinetic data the energies of activation, the pre-exponential factors and the reference values at 40 deg C were calculated.The rate of hydrolysis shows to be strongly dependent on the C-terminal amino acid in the sequence Gly >> Ala/Met/Phe > Leu >> Val/Pro.Surprisingly the N-terminal amino acid also exerts an effect, but in a different sequence.N-Terminal Phe in particular shows a relative accelerating effect.Remarkable is the significantly faster ester hydrolysis of glycine containing dipeptide ethyl esters in ethanol/water compared to the corresponding methyl esters in methanol/water.
Activation of Dithiocarbamate by 2-Halothiazolium Salts
Sugimoto, Hirohiko,Makino, Itsuo,Hirai, Kentaro
, p. 2263 - 2267 (2007/10/02)
Activation of dithiocarbamate salts with 2-halo-3-alkyl-4-phenylthiazolium salt and subsequent one-pot nucleophilic reaction with N, S, and O nucleophiles provided substituted thioureas, dithiocarbamates, and thiocarbamates or amides, respectively, under very mild conditions.A useful thiocarbonyl-transfer reaction is also described that consists of activation of imidazolodithiocarbamate and a subsequent one-pot nucleophilic reaction. (Thiocarbonyl)diimidazole is generated in situ.
Peptide Synthesis with Benzo- and Naphthosultones
Acher, Francine,Wakselman, Michel
, p. 4133 - 4138 (2007/10/02)
6-Nitro- and 6,8-dinitronaphth-1,2-oxathiole S,S-dioxides (7b and 7c) have been prepared from the parent naphthosultone 7a and compared with 5-nitrobenz-3H-1,2-oxathiole S,S-dioxide (1b) as coupling reagents for peptide synthesis.Nucleophilic attack of a carboxylate salt on these strained five-membered sultones leads to activated esters 3 and 9 which rapidly react with amines (except in the case of 9c).The rate constant for the formation of ester 9b is higher than that of 3b.Amides or peptides are formed in slightly better yields with the naphthosultone 7b than with the benzosultone 1b.The naphthosultones are also preferred over the benzosultones from the point of view of amount of 5(4H)-oxazolone formation from N-benzoyl amino acids and the degree of racemization.However the rate of alkaline hydrolysis of 7b is slower than that of 1b.All these results may be rationalized by a better intramolecular acyl transfer reaction in the more rigid mixed anhydride intermediate 8b.There is no dependence on in the rate equation for aminolysis of esters 3b and 9b by benzylamine in THF, acetonitrile, or DMF and the aminolysis is probably anchimerically assisted by a neighbouring S=O group.Esters 3b are more selective acylating agents for primary amino groups in the presence of secondary ones than esters 9b and this observation is exploited in a synthesis of maytenine by selective acylation of spermidine.
