Dipeptide Esters Research Articles

Binary and ternary complexes of platinum(II) with the dipeptide esters gly-glyOEt, gly-alaOMe, gly-2-abaOMe, gly-nvalOMe, gly-nleuOMe, and the nucleosides guo (guanosine) and cyd (cytidine)

Abstract The binary complexes of formulae cis -(dipeptide) 2 PtCl 2 and the ternary complexes of formulae cis -[(guo) 2 Pt(dipeptide) 2 ]Cl 2 and cis -[(cyd) 2 Pt(dipeptide) 2 ]Cl 2 , with guo=guanosine, cyd=cytidine, dipeptide=glyglyOEt, gly-l-alaOMe, gly-2-l-abaOMe, gly-l-nvalOMe, gly-l-nleuOMe, were isolated and characterized by elemental analysis, conductivity measurements, 1 H, 13 C NMR and IR spectroscopy. The binary complexes were obtained by the reaction of K 2 PtCl 4 with the dipeptide esters and the ternary ones by further reactions of the binary complexes with the corresponding nucleosides. The dipeptides are monocoordinated through their amino groups with Pt 2+ . Ligand–ligand hydrophobic interactions were observed to decrease with distance from the bonding sites. The percentages of the 3 E and anti conformations of the nucleosides increase, while the gg ones decrease in the complexes. Finally, the h conformers around the –CHα–CHβR– bonds of the peptides decrease on passing to the ternary from the binary system and increase with longer aliphatic chains.

2‐Benzoyl‐2‐ethoxycarbonylvinyl‐1 and 2‐benzoylamino‐2‐methoxy‐carbonylvinyl‐1 as N‐protecting groups in peptide synthesis. Their application in the synthesis of dehydropeptide derivatives containing N‐terminal 3‐heteroarylamino‐2,3‐dehydroalanine

AbstractEthyl 2‐benzoyl‐3‐dimethylaminopropenoate (6) and methyl 2‐benzoylamino‐3‐dimethylaminopropenoate (46) were used as reagents for the protection of the amino group with 2‐benzoyl‐2‐ethoxycarbonylvinyl‐1 and 2‐benzoylamino‐2‐methoxycarbonylvinyl groups in the peptide synthesis. Reactions of ethyl 2‐benzoyl‐3‐dimethylaminopropenoate (6) with α‐amino acids gave N‐(2‐benzoyl‐2‐ethoxycarbonylvinyl‐1)‐α‐amino acids 13–19. These were coupled with various amino acid esters to form N‐(2‐benzoyl‐2‐ethoxycar‐bonylvinyl‐1)‐protected dipeptide esters 20–31. The removal of 2‐benzoyl‐2‐ethoxycarbonylvinyl‐1 group, which was achieved by hydrazine monohydrochloride or hydroxylamine hydrochloride, afforded hydrochlo‐rides of dipeptide esters 32–41 in high yields. Similarly, the substitution of the dimethylamino group in methyl 2‐benzoylamino‐3‐dimethylaminopropenoate (46) by glycine gave N‐(2‐benzoylamino‐2‐methoxycar‐bonylvinyl‐1)glycine (47), which was coupled with glycine ethyl ester to give N‐[N‐(2‐benzoylamino‐2‐methoxycarbonylvinyl‐1)glycyl]glycine ethyl ester (48). Treatment of 48 with 2‐arnino‐4,6‐dirnethylpyrimi‐dine afforded N‐[glycyl]glycine ethyl ester hydrochloride (34) in high yield. Amino acid esters and dipeptide esters were employed in the preparation of tri‐ 58‐70, tetra‐ 71–82, and pentapeptide esters 83–85 containing N‐terminal 3‐heteroarylamino‐2,3‐dehydroalanine. 2‐Chloro‐4,6‐dimethoxy‐1,3,5‐triazine was employed as a coupling reagent for the preparation of peptides 58–85.

エナンチオマーおよびジアステレオマーエステル不斉加水分解の立体制御‐超分子集合体の新しい展開

The remarkably high enantioselectivity (k, La, obsd/kDa, obsd = 1000) was attained for the hydrolysis of amino acid esters (N-dodecanoyl-D (L) -phenylalanine p-nitrophenyl ester; C12-D (L) -Phe-PNP) catalyzed by the active tripeptide (N- (benzyloxycarbonyl) -L-phenylalanyl-L-histidyl-L-leucine; Z-Phe-His-Leu) in the coaggregate systems composed of 41 mol% hexadecyltrimethylammonium bromide (CTAB) and 59 mol% ditetradecyldimethylammonium bromide (2 C14Br) at the specific ionic strength (μ =0.02). With respect to the temperature dependence of hydrolysis in the coaggregate systems composed of native lipid (L-α-dipalmitoylphosphatidylcholine; DPPC) and nonionic surfactant (α- [4- (1, 1, 3, 3- tetramethylbutyl) phenyl] -ω-hydroxydecakis (oxyethylene); Triton X-100), the enantioselectivity was maximized at the phase transition temperature (Te) and the hydrophobic microenvironment of coaggregates could be evaluated on the basis of isokinetic temperature (β). On the other hand, in the stereoselective hydrolysis of dipeptide esters as mediated by cyclodextrins (CyD), a high diastereoselectivity (kDL2/kLL2 =46) and preferential binding property (KDLb/KLLb= 2.4) were observed for the hydrolysis of N- (benzyloxycarbonyl) -D (L) -phenylalanyl-L-phenylalanine p-nitrophenyl ester (Z-D (L) -Phe-L-Phe-PNP) by γ-CyD. Furthermore, the computer modeling (MOPAC calculation) study suggests that a favorable molecular recognition between the substrate and catalyst through the effective hydrophobic interactions and hydrogen bonds should be very important for the enhancement of stereoselectivity.

Organometallic Half‐Sandwich Complexes Promote the Formation of Linear Oligopeptides from Amino Acid Esters

AbstractOrganometallic dipeptide ester complexes of the general formula [(L)M(Cl)(K2‐NH2CH2CONCH2CO2R)] (1: LCp*, MRh, 2: LCp*, MIr, 3: Lη6‐C6Me6, MRu) react smoothly with various α‐L‐amino acid esters in the presence of NEt3 to yield the tripeptide ester complexes [(L)M(Cl)(K2‐NH2CHR'CONCH2CONHCH2CO2R)] (5–7). In the same fashion chloro K2‐tetrapeptide ester complexes 10 and 11 are obtained either from tripeptide ester complexes or by subsequent addition of two equivalents of amino acid ester to a dipeptide ester complex. When the strong base NaOMe is used in the reaction of the diglycine ester compounds with amino acid esters. K3‐tripeptide ester complexes 12 and 13 are produced, in which one of the two coordinated peptide nitrogen atoms is pyramidal. The hexamethylbenzene ruthenium complexes 13 with tripeptide ligands are formed with very high diastereoselectivity. A plausible reaction mechanism for the metal‐promoted peptide synthesis is presented. Synthesis and isolation of the peptide esters proceeds without racemization.

A new simple route to the synthesis of protease substrates in ice

Abstract The serine proteases α-chymotrypsin and trypsin and the cysteine protease papain were used to catalyze the synthesis of Nα-protected di- and tripeptide ester substrates by acyl transfer of the corresponding Nα-protected amino acid esters to various amino acid- or dipeptide esters. The very simple and economical strategy benefits from performing the enzymatic reaction in frozen-aqueous systems. The products, which can further act as specific substrates for several important proteases, are obtainable in high yields and can be isolated easily. The results show an extraordinary shift in S' specificty of the proteases in frozen aqueous systems and are of general importance for protease-directed step-by-step peptide synthesis with a minimal protection/deprotection techniques.

A remarkably enhanced diastereoselectivity for the hydrolysis of dipeptide esters responding to pH and temperature in buffer solutions

The remarkable high diastereoselectivity for the hydrolysis of Z-D(L)-Phe-L-Phe-PMCP ( DL LL = 40 ) or Z-D(L)-Phe-L-Phe-PNP ( DL LL = 130 ) was attained by regulating pH and temperature in buffer solutions.

Selective deprotection of phenacyl, benzyl and methyl esters of N-protected amino acids and dipeptides and N-protected amino acids benzyl ester linked to resins with bis(tributyltin) oxide

Phenacyl, methyl and benzyl esters of variousN-α-Boc, N-α-Cbz or N,N-dimethylamino protected amino acids and dipeptides, as well as esters of N-α-protected amino acids linked to Wang and Pam resins have been efficiently and chemoselectively cleaved by bis(tributyltin) oxide in aprotic solvents to give the corresponding carboxylic acids in good yields. Moreover, the absence of racemization during the deprotection has been demonstrated. A limitation of the method is the instability of the N-Iµ-Fmoc group in the amino acid esters 8 and 10, N-α-Fmoc-L-alanine linked to Wang resin 23 and the Cbz protecting groups in N-α-Boc-N-Iµ-Cbz-L-lysine benzyl and methyl esters (5 and 7), respectively, and N-α-Cbz-L-alanyl-L-alanine methyl ester 19. In the case of N-α-protected dipeptides, there was no evidence of free amino acid which indicates that the peptide bond is unaffected.

Subtilisin and α-chymotrypsin catalyzed synthesis of peptides containing arginine and lysine p-nitroanilides as c-terminal moieties

p-Nitroanilides of N-acylated di-, tri- and tetrapeptides with C-terminal arginine or lysine residues have been obtained, as a rule with good yields, via acylation of arginine or lysine p-nitroanilides by methyl esters of respective N-acylated peptides, catalyzed by subtilisin or α-chymotrypsin. The synthesis might be performed by two routes-by reaction in water-organic solvent mixtures, catalyzed by dissolved enzyme, or by condensation of the components in organic solvents with low water content in the presence of any enzyme distributed over a silica support surface. The second approach seems to be preferable due to suppression of hydrolytic side reactions and improved stability of an enzyme. Subtilisin 72 is especially effective as a catalyst for the acylation of p-nitroanilides by N-protected tripeptide methyl esters-the derivatives capable of occupying the S 1, S 2 and S 3 subsites of its extended binding site. Even dipeptide esters with d-amino acids in P 2 position can be applied for p-nitroanilide acylation. The efficiency of α-chymotrypsin as a catalyst for peptide synthesis is more limited due to restricted specificity of this enzyme.

Chromatographic Studies on the Racemization of Thiopeptides

Abstract It was found by chromatographic, CD and NMR methods, that the thionation of piperazine-2,5-diones [cyclo(Aaa1-Aaa2) → cyclo (Aaat 1-Aaat 2 (Aaa=-NH-CHR-CO-; Aaat=-NH-CHR-CS-)] or piperazine-2,5-onthiones [cyclo(Aaat 1-Aaa2) → cyclo (Aaat-Aaat)] and, occasionally, even the spontaneous cyclization of endo-thiodipeptide esters [H-Aaat-Aaa-OR] result in enantiomeric (Aaa or Aaa=Gly) or diastereomeric mixtures of piperazine monothiones or dithiones. The diastereoisomers were separated by semipreparative HPLC and their quantitative product distribution was determined by an optimized HPLC method on Hypersil-silica column with CH2Cl2-EtOAc eluent mixtures. Isocratic RP-HPLC on ODS-Hypersil column and pre-column derivatization with 1-flu-oro-2,4-dinitrophenyl-5-L-alanine amide (Marfey's reagent) were used to monitor the racemization of Ala and Pro residues and to determine the ratio of enantiomers. Thionation of urethane protected dipeptide esters or dethionation of the corresponding endoth-iodipeptide de...

Untersuchungen zur Kn�pfung der Peptidbindung mit ?-trifluormethylsubstituierten ?-Aminos�uren

Chemical Peptide Bond Formation with α-Trifluoromethyl Substituted α-Amino Acids The reaction of α-trifluoromethyl substituted N-tbutoxycarbonyl amino acids (Boc-TFM-Xaa-OH) 1 with dicyclohexylcarbodiimide results in formation of 2-tbutoxy-4-trifluoromethyl-5(4H)-oxazolones 2 within minutes. Compounds 2 react with amino acid esters to give Boc protected dipeptide esters 4. However, at room temperature compounds 2 decompose to give Leuchs anhydrides 3, via retro ene reaction. Therefore, α-trifluoromethyl substituted N-tbutoxycarbonyl amino acids (Boc-TFM-Xaa-OH) are of limited value for peptide synthesis.

A facile conversion of arginine into β-homoarginine dipeptides

Irradiation of the arginine derived diazomethyl ketone 2 in the presence of amino esters gives the corresponding β-homoarginine dipeptide esters 3c–h in 45–76% yield.

Asymmetric synthesis of α-trifluoromethyl substituted aminoacids via 3-hydroxy-3-trifluoromethyl-2,5-diketopiperazines

The diastereoselective reaction of organometallic compounds (RMgX, R 2Cd) with in situ generated trifluoromethyl substituted cyclic acyl imines representing homochiral α-electrophilic 3,3,3-trifluoroalanine equivalents gives 3-alkyl-3-trifluoromethyl-2,5-diketopiperazines. The corresponding homochiral dipeptide esters are obtained on acidolysis in methanol.

Solution synthesis of a dimeric pentapeptide: Diketopiperazine cyclisation of Glu-Asp dipeptide esters and Asp-racemisation during segment condensation

A haemoregulatory peptide analogue derived from the cystine-dimerised pentapeptide Glp-Glu-Asp-Cys-Lys-OH, in which the cystine residue has been replaced by an isosteric L,L-2,7-diaminosuberic acid moiety, was prepared by segment condensation in solution. The preparation of protected Glp-Glu-Asp-OH tripeptides was found to be hampered by the surprising ease with which t-butyl side-chain protected H-Glu-Asp-OR dipeptide esters underwent diketopiperazine cyclisation. A number of Asp esters were compared in this respect. Reaction conditions for the segment condensation were investigated in terms of racemisation as well as chemical yield and product purity.

Temperature Control for the Diastereoselective Hydrolysis of Dipeptide Esters in the Buffer Solution.

A remarkably high stereoselectivity was attained for the hydrolysis of dipeptide p-nitrophenyl esters (DL/LL=101 for Z-Phe-Phe-PNP and DL/LL=71 for Z-Phe-Leu-PNP) without a catalyst in pH 9.5, 0.02 M carbonate buffer at the optimum temperature (32.5°C).

Kinetic characterization of affinity chromatography purified clostripain.

The cysteine protease clostripain, purified by affinity chromatography on a large scale, shows very high activity against BAEE using the titrimetric standard assay. Furthermore, titration of the active site with the irreversible inhibitor tosyl-lysyl-chloromethane resulted in a more than two times higher specific activity compared with literature data (Porter et al. (1971) J. Biol. Chem. 246, 7675-7682). Based on the molar enzyme concentration determined, the hydrolysis kinetics of the standard substrate BAEE were compared with those for the N alpha-protected dipeptide ester Mal-Tyr-Arg-OEt. It was demonstrated from the kinetic data that the highly purified clostripain is the most active enzyme preparation available up to now. In contrast to the standard substrate, Mal-Tyr-Arg-OEt shows a threefold lower specificity constant.

Degradable polyphosphazenes for biomedical applications

Polyphosphazene derivatives having amino acid ester side groups were prepared by reaction of poly (dichloro phosphazene) with ethyl esters of amino acids and dipeptides. In vitro degradation studies demonstrated that the rate of degradation depends on the nature of the amino acids. Introducing small amounts of depsipeptide ester co-substituents resulted in a drastic increase of the degradation. The rate of hydrolytic degradation of the polyphosphazene materials could be controlled by the content of the depsipeptide ester side groups or by blending poly [amino acid ester) phosphazenes] with poly [(amino acid ester)-co-(depsipeptide ester) phosphazenes]. A more detailed study of the degradation process indicated that in the initial stage of polymer degradation the amino acid ethyl ester is released, with subsequent formation of amino acid, ethanol and polymer backbone cleavage. Polyphosphazenes substituted with ethyl glycinate (D.S. 99%) are partially crystalline. D.S.C. experiments demonstrated that the degree of crystallinity and the morphology of the crystalline phase depends on the storage conditions.

Peptide production by a combination of gene expression, chemical synthesis, and protease-catalyzed conversion.

We describe a new approach for the production of peptides using a combination of recombinant DNA technology, chemical synthesis, and proteinase-catalyzed processing. An artificial substance P-precursor is produced as a beta-galactosidase (1-459) fusion protein containing nine copies of the decapeptide sequence Arg-Leu-Arg-Arg-Pro-Lys-Pro-Gln-Gln-Phe. The fusion protein accumulates in E. coli as insoluble inclusion bodies which are easily isolated and purified. The decapeptide blocks are selectively cleaved from the insoluble fusion protein by alpha-chymotrypsin. Alternatively, a dodecapeptide ester is produced when a dipeptide ester is included in the chymotrypsin reaction mixture. This peptide ester is converted converted to substance P by papain-catalyzed acyl transfer and subsequent tryptic cleavage. These results demonstrate that peptides can be readily produced by a combination of recombinant DNA technology and proteinase-catalyzed conversion. The approach allows incorporation of groups other than natural amino acids into oligo- and polypeptides.

Absolute configurations and conformations of sweet and tasteless aminomalonyl (Ama) dipeptide esters: Ama-Phe-OMe and Ama-Phe-OEt

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAbsolute configurations and conformations of sweet and tasteless aminomalonyl (Ama) dipeptide esters: Ama-Phe-OMe and Ama-Phe-OEtToshihiko Ando, Masafumi Ota, Tatsuki Kashiwagi, Nobuya Nagashima, Yasuo Ariyoshi, Raj K. Chadha, Toshimasa Yamazaki, and Murray GoodmanCite this: J. Am. Chem. Soc. 1993, 115, 2, 397–402Publication Date (Print):January 1, 1993Publication History Published online1 May 2002Published inissue 1 January 1993https://doi.org/10.1021/ja00055a005RIGHTS & PERMISSIONSArticle Views92Altmetric-Citations9LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (794 KB) Get e-AlertsSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts

General methods for .alpha.- or .beta.-O-Ser/Thr glycosides and glycopeptides. Solid-phase synthesis of O-glycosyl cyclic enkephalin analogs

O-Linked glycopeptides have been efficiently synthesis using the highly nucleophilic α-imino esters (O'Donnell's Schiff bases) derived from L-serine (3a-c), L-threonine (4a,b), and a dipeptide ester (5). General methodology has been developed which can provide β-glycosides of β-hydroxy-α-amino acid derivatives 6-16 in excellent yield (63-94%) and excellent selectivity (>20:1) using Hanessian's modification or Helferich's modification of the Koenigs-Knorr reaction.Likewise,selective α-glycosylation has been achieved using the in situ anomerization methodology of Lemieux.The increased nucleophilicity of the serine/threonine hydroxyl has been shown to be due to intramolecular hydrogen bonding to the N=CPh 2 moiety.Deprotection of the intermediate Schiff bases has been demonstrated ,and the glycosides have been incorporated into fully deprotected O-linked glycopeptides in high yield using either solution-phase peptide methods or solid-phase Fmoc-based technology.An potent glycosylenkephalin analogue has been prepared using the solid-phase methodology

A peptide-aluminum complex as a novel chiral Lewis acid. Asymmetric addition of cyanotrimethylsilane to aldehydes

The enantioselective addition of cyanotrimethylsilane (TMSCN) to aldehydes promoted by the addition of a stoichiometric or catalytic amount of organoaluminum complexes of dipeptide esters or α-amino acid amides whose amino terminals are modified by a variety of protective groups is described.These compounds serve as ligands for chiral Lewis acid catalysts