- N,O-Bis(trimethylsilyl)acetamide/N-hydroxysuccinimide ester (BSA/NHS) as coupling agents for dipeptide synthesis
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A method using N,O-bis(trimethylsilyl)acetamide/N-hydroxysuccinimide ester (BSA/NHS) as coupling agents for dipeptide synthesis is descried. The coupling reaction between N-hydroxysuccinimide (NHS) esters and amines could be performed under mild conditions with N,O-bis(trimethylsilyl)acetamide (BSA) as coupling reagent and no additional acid/base is required. All byproducts and excessive reactants are water soluble or hydrolysable and easy to eliminate through water-washing at the purification stage. Moreover, all the reactants are inexpensive and widely used in conventional drug production.
- Huang, Ye,Feng, Wen-Hua
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Read Online
- Synthesis of 5(S)-Methyl-L-Proline Containing Peptidomimetic Compounds and their In Vitro Evaluation for Dipeptidyl Peptidase-4 Inhibition
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Background: Type 2 diabetes mellitus (T2DM), which is the epidemic of the 21st century, has affected millions of people worldwide. Traditional methods available for the treatment are associated with various side effects. Among the newer therapies, DPP-4 (Dipeptidyl peptidase-4) inhibition has been a promising therapy for the past decade with the scope of further development, especially in peptidomimet-ics. Objective: 5(S)-methyl-L-proline containing peptidomimetic compounds were designed in the previous work. The designed compounds were synthesized and characterized by spectral methods, such as mass spectrometry,1H NMR, and13C NMR (Nuclear magnetic resonance) spectroscopy. The purity of the final compounds was determined by high-performance liquid chromatography (HPLC). The synthesized compounds were in vitro evaluated for their DPP-4 inhibitory activity. Methods: Compounds were peptide in nature and were synthesized using the conventional synthesis ap-proach, where peptide synthesis was done using an acid-amine coupling reagent. They were evaluated through fluorimetric enzyme-based assay using a DPP-4 inhibitor screening kit. Moreover, the CLARIO-star microplate reader instrument was used to measure fluorescence. Results: 5(S)-methyl-L-proline containing 13 compounds were synthesized. All of them were characterized for structural integrity using spectral methods. They had HPLC purity of more than 95% and were evaluated for DPP-4 inhibition. Compounds 1, 7, 10, 11, 14 and 17 were found to have good inhibition than others. These compounds were further evaluated at different concentrations to develop a linear corre-lation coefficient (R2). Conclusion: Six compounds were found to have good DPP-4 inhibition, hence it further opens the possi-bility of developing DPP-4 inhibitor-containing 5(S)-methyl-L-proline.
- Gajjar, Anuradha K.,Pathak, Chirag D.
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p. 350 - 365
(2022/05/12)
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- Photoredox-Mediated Reaction of gem-Diborylalkenes: Reactivity Toward Diverse 1,1-Bisborylalkanes
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The use of gem-diborylalkenes as radical-reactive groups is explored for the first time. These reactions provide an efficient and general method for the photochemical conversion of gem-diborylalkenes to rapidly access 1,1-bisborylalkanes. This method expl
- Eghbarieh, Nadim,Kumar, Nivesh,Masarwa, Ahmad,Shames, Alexander I.,Stein, Tamar
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p. 5360 - 5364
(2020/04/23)
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- Chemical profiling of HIV-1 capsid-targeting antiviral PF74
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The capsid protein (CA) of HIV-1 plays essential roles in multiple steps of the viral replication cycle by assembling into functional capsid core, controlling the kinetics of uncoating and nuclear entry, and interacting with various host factors. Targetin
- Casey, Mary C.,Do, Ha T.,Du, Haijuan,Hachiya, Atsuko,Kirby, Karen A.,Sahani, Rajkumar Lalji,Sarafianos, Stefan G.,Tedbury, Philip R.,Vernekar, Sanjeev Kumar V.,Wang, Lei,Wang, Zhengqiang,Xie, Jiashu,Zhang, Huanchun
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- Inhibition of urease enzyme activity by urea and thiourea derivatives of dipeptides conjugated 2, 3-dichlorophenyl piperazine
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Objective: Studies on enzyme inhibition remain an important area of pharmaceutical research since these studies have led to the discoveries of drugs used in a variety of physiological conditions. In search of novel urease enzyme inhibitors, four dipeptide
- Suyoga Vardhan,Kumara,Pavan Kumar,Channe Gowda
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- Synthesis of cytotoxic cyanobactin, Wewakazole B
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We report herein the synthesis of cytotoxic cyanobactin, Wewakazole B through an efficient solution-phase approach. The key steps of the synthesis are the macrocyclic lactamization of linear dodecapeptide and construction of two hexapeptides with three di
- Nayani, Kiranmai,Anwar Hussaini
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p. 1166 - 1169
(2017/03/02)
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- Total Synthesis of the Cyclic Dodecapeptides Wewakazole and Wewakazole B
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The cyclic dodecapeptides wewakazole and wewakazole B have been synthesized by a divergent strategy via a common tris-proline containing oxazole octapeptide and two separate bis-oxazole containing tetrapeptide units, followed by peptide coupling and macro
- Inman, Martyn,Dexter, Hannah L.,Moody, Christopher J.
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p. 3454 - 3457
(2017/07/15)
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- Total synthesis of cyclic heptapeptide Rolloamide B
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The first total synthesis of Rolloamide B, a cyclic proline-enriched heptapeptide, is reported. This work features solution phase benzotriazole-mediated peptide synthesis ligating native amino acids. The Royal Society of Chemistry 2013.
- Khatib, Mirna El,Elagawany, Mohamed,?ali?kan, Eray,Davis, Emily Faith,Faidallah, Hassan M.,El-Feky, Said A.,Katritzky, Alan R.
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supporting information
p. 2631 - 2633
(2013/05/08)
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- Synthesis, docking and anticancer activity studies of D-proline- incorporated wainunuamide
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D-proline-incorporated wainunuamide - a cyclic octapeptide was synthesized and characterized by FTIR, 1H and 13C NMR and Mass spectral analysis. Molecular docking studies were carried out for the designed cyclic octapeptide and the results showed greater affinity for HPV18-2IOI receptor (HeLa cancer cell line). The synthesized cyclic octapeptide exhibited potent anticancer activity against HeLa cancer cells. Indian Academy of Sciences.
- Himaja,Ranjitha,Mali, Sunil V.
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p. 1049 - 1055
(2013/03/13)
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- Total synthesis and antimicrobial activity of a natural cycloheptapeptide of marine origin
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The present study deals with the first total synthesis of the proline-rich cyclopolypeptide stylisin 2 via a solution phase technique by coupling of the Boc-L-Pro-L-Ile-L-Pro-OH tripeptide unit with the L-Phe-L-Pro-L-Pro-L-Tyr-OMe tetrapeptide unit, follo
- Dahiya, Rajiv,Gautam, Hemendra
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scheme or table
p. 2384 - 2394
(2010/10/20)
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- Antimicrobial activity, biocompatibility and hydrogelation ability of dipeptide-based amphiphiles
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The development of new antibiotics is of increasing importance due to the growing resistance power of microbes against conventional drugs. To this end, cationic peptides are emerging as clinically potent antimicrobial agents. In the present study, we have
- Mitra, Rajendra Narayan,Shome, Anshupriya,Paul, Pritha,Das, Prasanta Kumar
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experimental part
p. 94 - 102
(2009/04/07)
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- Total synthesis and biological potential of psammosilenin A
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The present work reports the synthesis of a plant-originated cyclooctapeptide - psammosilenin A 8 by cyclization of linear peptide fragment phe-pro-phe-phe-ala-pro-leu-pro-Opfp which was prepared by coupling of tetrapeptide units Boc-phe-pro-phe-phe-OH an
- Dahiya, Rajiv
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experimental part
p. 502 - 509
(2009/04/04)
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- Molecular design and structure - Activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664
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A series of structurally novel small molecule inhibitors of human α-thrombin was prepared to elucidate their structure-activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human α-thrombin which is efficacious in vivo in a mouse lethality model, and at inhibiting both arterial and venous thrombosis in cynomolgus monkey models.
- Das, Jagabandhu,Kimball,Hall, Steven E.,Han, Wen-Ching,Iwanowicz, Edwin,Lin, James,Moquin, Robert V.,Reid, Joyce A.,Sack, John S.,Malley, Mary F.,Chang, Chiehying Y.,Chong, Saeho,Wang-Iverson, David B.,Roberts, Daniel G.M.,Seiler, Steven M.,Schumacher, William A.,Ogletree, Martin L.
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- Total synthesis and conformational studies of ceratospongamide, a bioactive cyclic heptapeptide from marine origin
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The first total synthesis of cis,cis-ceratospongamide (cyclo[L-Pro-L-Ile-Me-oxazoline-L-Phe-L-Pro-thiazole-L-Phe-]) was accomplished and confirmed by X-ray crystal analysis. The heating of cis,cis-ceratospongamide in DMSO converted it not to the trans,trans isomer but to the trans,trans-[D-allo-Ile]-ceratospongamide, which was confirmed by total synthesis. Its solution conformation was constructed by the dynamic simulated annealing method using ROE cross peaks, revealing a rounded and flat ring structure which is in contrast with the slim and tight structure of cis,cis isomer. The results shows that the trans,trans-[D-allo-Ile] isomer is the main thermal product of cis,cis-ceratospongamide.
- Yokokawa, Fumiaki,Sameshima, Hirofumi,In, Yasuko,Minoura, Katsuhiko,Ishida, Toshimasa,Shioiri, Takayuki
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p. 8127 - 8143
(2007/10/03)
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- Synthesis and kinetics of oxidation of some dipeptides with anodically generated manganese(III) sulphate: Mechanistic study
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Dipeptides (DP) namely phenylalanyl-proline (Phe-Pro), isoleucyl-proline (Ile-Pro), and leucyl-proline (Leu-Pro) were synthesized by classical solution method and characterized. The kinetics of oxidation of these DP by Mn(III) have been studied in the presence of sulphate ions in acidic medium at 26°C. The reaction was followed spectrophotometrically at λmax = 500 nm. A first-order dependence of rate on both [Mn(III)]0 and [DP]0 was observed. The rate is independent of the concentration of reduction product, Mn(II), and hydrogen ions. The effects of varying dielectric constant of the medium and addition of anions such as sulphate, chloride, and perchlorate were studied. The activation parameters have been evaluated using Arrhenius and Eyring plots. The oxidation products were isolated and characterized. A mechanism involving the reaction of DP with Mn(III) in the rate-limiting step is suggested.
- Kumara,Channe Gowda,Rangappa
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p. 438 - 444
(2007/10/03)
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- Total synthesis of cis,cis-ceratospongamide, a bioactive thiazole-containing cyclic peptide from marine origin
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The first total synthesis of cis,cis-ceratospongamide (1a), isolated from marine source, was accomplished via thiazole synthesis using CMD methodology, DEPC-mediated peptide coupling, macrolactamization, and cyclodehydration. Comparison of the cyclization sites and coupling reagents in the macrolactamization step was also investigated.
- Yokokawa,Sameshima,Shioiri
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p. 986 - 988
(2007/10/03)
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- Efficient, non-acidolytic method for the selective cleavage of N-Boc amino acid and peptide phenacyl esters linked to a polystyrene resin
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An efficient, non-acidolytic method for the selective cleavage of phenacyl esters of N-Boc-amino acids and -peptides linked to a polystyrene resin by (CH3)3SnOH (TMTOH) or [(n-C4H9)3Sn]2O (BBTO) is described. We highly recommend the use of trimethyltin hydroxide for the selective cleavage of carboxylic esters based on its favourable properties. The method is compatible with an N-Boc/O-Bn (benzyl ether) strategy and yields enantiomerically pure N-Boc-peptides useful for further manipulation, for segment condensations or for cyclization strategies. A mechanism for the cleavage of methyl phenylacetate in solution by TMTOH is postulated.
- Furlan, Ricardo L. E.,Mata, Ernesto G.,Mascaretti, Oreste A.
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p. 355 - 358
(2007/10/03)
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- Synthesis and biological activity of branched enkephalin analogues
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The synthesis and biological activity of a new type of enkephalin analogs are reported. A series of branched pentapeptides of the enkephalin sequence with replacement of 2-glycine by D-ornithine and branching of the peptide chain in position 2 by attachment of proline, leucine, asparagine or methionine residues to the 8-amino group of D-ornithine were synthesized by classical solution methodology. Analgesic activity of the new analogs was assayed by the 'tail pinch' method following intracisternal and intravenous administrations to mice. They showed higher analgesic potency and longer duration of action as compared to linear and cyclic pentapeptides with the same amino acid composition. The activity determined in the GPI and MVD bioassays, and in a binding assay, revealed the preference of the branched analogs for the μ-type of opioid receptor over the δ-type. These results raise the possibility to synthesize enkephalin analogs with high analgesic potency and opiate receptor selectivity by varying the chemical character and length of the side chain in the 2-position.
- Bobrova, Irina,Abissova, Natalia,Mishlakova, Natalia,Rozentals, Guntis,Chipens, Gunar
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p. 255 - 266
(2007/10/03)
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- Exclusive affinity-labeling of μ opioid receptors by morphiceptin analogs containing S-(3-nitro-2-pyridylthio)cysteine
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The S-(3-nitro-2-pyridylthio) (Npys) group only reacts with a free mercapto group to form a disulfide bond. A series of morphiceptin analogs containing SNpys-cysteine were designed and synthesized for specific affinity-labeling of μ opioid receptors. Affi
- Motoyama, Shihoko,Takada, Kiyoshi,Yasunaga, Teruo,Fujita, Tsugumi,Shimohigashi, Yasuyuki
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p. 3607 - 3612
(2007/10/03)
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- 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
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Phenacyl, methyl and benzyl esters of various N-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-ε-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-ε-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.
- Salomon, Claudio J.,Mata, Ernesto G.,Mascaretti, Oreste A.
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p. 995 - 999
(2007/10/03)
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- Synthesis of a Cyclic Analog of Enkephalin with Prolonged Analgesic Action
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A cyclic analog of enkephalin, cyclo(Lys-Tyr-D-Met-Gly-Phe-Pro-) and two corresponding linear hexapeptides with an N- or C-terminal lysine residue, Lys-Tyr-D-Met-Gly-Phe-Pro and Tyr-D-Met-Gly-Phe-Pro-, were synthetized by standard and solid-phase
- Bobrova, I. V.,Myshlyakova, N. A.,Papsuevich, O. S.,Vosekalna, I. A.,Mekshun, E. I.
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p. 236 - 241
(2007/10/02)
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- Conformational studies of cyclo(L-Phe-L-Pro-Gly-L-Pro)2 by 1H- and 13C-nuclear magnetic resonance spectroscopy, and its enantioface-differentiating ability
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Analyses of the 1H- and 13C-nuclear magnetic resonance (1H- and 13C-NMR) spectra of the cyclooctapeptide cyclo (L-Phe-L-Pro-Gly-L-Pro)2 (3) in CDCl3 with the aid of the C-H correlated spectroscopy (C-H COSY) two-dimensional NMR spectrum (Fig. 2) suggested that two kinds of C2-symmetric conformation with all trans and cis-trans-trans-trans forms coexist. When 0.5 eq of CsSCN or 1 eq of D- and L-PheOMe · HCl (D/L ratio = 1/2) was added to a solution of the cyclooctapeptide (3) in CDCl3, the 1H- and 13C-NMR spectra (Fig. 3) suggested the presence of only one C2-symmetric conformation (all trans), resulting from the formation of complexes with CsSCN or D- and L-PheOMe · HCl. The 13C-NMR spectra of the complexes of the cyclooctapeptide (3 or 4) with D- and L-PheOMe · HCl displayed separate resonances for each carbon atom of D-PheOMe · HCl and L-PheOMe · HCl. Furthermore, the ability of 3 to distinguish the D from the L enantiomer, is superior to that of 4 (Table II).
- Ishizu,Fujii,Noguchi
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p. 235 - 238
(2007/10/02)
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- Conformational studies of cyclo(L-Phe-L-Pro-Gly-L-Pro)2 by 13C nuclear magnetic resonance
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The 13C-NMR spectrum of cyclooctapeptide cyclo(L-PHe-L-Pro-Gly-L-Pro)2 (A) in CDCl3 suggested that its conformation involved the coexistence of two kinds of C2-symmetric conformation with trans-trans-trans-trans
- Ishizu,Fujii,Noguchi
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p. 1617 - 1619
(2007/10/02)
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- Peptides
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A peptide of formula (I): wherein X represents hydrogen, or a terminal nitrogn protecting group selecting from the group consisting of the acyl, aromatic oxycarbonyl, alkyl, aralkyl and aliphatic oxycarbonyl; A represent a valence bond or a L-α-amino acid residue; B represent a L-α-imino acid residue or a L-α-amino acid; C represent a L-α-imino acid residue or a neutral L-α-amino acid residue; D represents a valence bond or a L-α-amino acid residue; and Y represents hydroxy, an amino group or a group of the formula OR, NHR, NR2 or NH--NH--R', wherein R represents a straight chain, branched chain or cyclic (including fused or bridged ring) alkyl group having up to 11 carbon atoms, optionally being substituted; a phenyl group or an aralkyl group having from 7 to 9 carbon atoms; and R' represents hydrogen, any of the groups which R may represent; a straight chain, branched chain or cyclic aliphatic acyl group having from 1 to 11 carbon atoms, optionally substituted by hydroxy, an amino group or a halogen atom; an aromatic acyl group, optionally substituted by hydroxy, amino, or a halogen atom; a straight chain, branched chain or cyclic aliphatic oxycarbonyl group having from 3 to 11 carbon atoms, or an aromatic oxycarbonyl group.
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- Bitter Taste of Synthetic C-Terminal Tetrapeptide of Bovine β-Casein, H-Pro196-Val-Leu-Gly-Pro-Arg-Gly-Pro-Phe-Pro-Ile-Ile-Val209-OH, and Its Related Peptides
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The primary structure of bovine β-casein contains the partial sequence of -Pro196-Val-Leu-Gly-Pro-Val-Arg-Gly-Pro-Phe-Pro-Ile-Ile-Val209 in the C-terminal portion.We previously reported that the synthetic C-terminal octapeptide, Arg202-Val209, is extremly bitter with its threshold value 0.004 mM, 250 times as strong as that of caffeine.To further investigate the bitter taste of the C-terminal portion of β-casein, we synthesized the C-terminal tetrapeptide, Pro196-Val209, and some its fragments.A hydrophobic hexapeptide, Pro196-Val201, was twice as bitter as caffein.The bitter taste of decapeptide, Pro200-Val209, was the same as that of Arg202-Val209.Although the tetradecapeptide, Pro196-Val209, was composed of two bitter peptides, Pro196-Val201 and Arg202-Val209, its bitter taste was weaker than that of Arg202-Val209 and its threshold value was 0.015 mM.We suggested that the increase of bitterness in peptides through the introduction of hydrophobic amino acids depended on the number of hydrophobic amino acids added.In addition, the synthetic retro analog of Arg202-Val209 (H-Val-Ile-Ile-Pro-Phe-Pro-Gly-Arg-OH) was not as bitter as Arg202-Val209.This indicated that the sequence of Arg202-Val209 is important for extreme bitterness.
- Shinoda, Ichizo,Fushimi, Akira,Kato, Hironobu,Okai, Hideo,Fukui, Sazuko
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p. 2587 - 2596
(2007/10/02)
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