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1.
JOHN W. PERICH 《Chemical biology & drug design》1994,44(3):288-294
The synthesis of the two 4-phosphono-2-aminobutanoyl-containing peptides, Leu-Arg-Arg-Val-Abu(P)-Leu-Gly-OH.CF3CO2H and Ile-Val-Pro-Asn-Abu(P)-Val-Glu-Glu-OH.CF3CO2H was accomplished by the use of Fmoc-Abu(PO3Me2)-OH in Fmoc solid-phase peptide synthesis. The protected phosphoamino acid, Fmoc-Abu(PO3Me2)-OH, was prepared from Boc-Asp-O'Bu in seven steps, the formation of the C—P linkage being effected by the treatment of Boc-Asa-O'Bu with dimethyl trimethylsilyl phosphite. Peptide synthesis was performed using Wang Resin as the polymer support with both peptides assembled by the use of PyBOP® for the coupling of Fmoc amino acids and 20%, piperidine for cleavage of the Fmoc group from the Fmoc-peptide after each coupling cycle. Cleavage of the peptide from the resin and peptide deprotection was accomplished by the treatment of the peptide-resin with 5%, thioanisole/TFA followed by cleavage of the methyl phosphonate group by 1 M bromotrimethylsilane/l M thioanisole in TFA. 相似文献
2.
During the benzyloxycarbonylation of H-Asp(OBzl)-OH by the Schotten-Bauman reaction with benzyloxycarbonyl chloride in the presence of NaHCO3 or Na2CO3, besides Z-Asp(OBzl)-OH, Z-Asp(OBzl)-Asp(OBzl)-OH was formed as side product, although the extent of the dipeptide formation differed depending on the base used (10% and 20% respectively). It was found that melting point, rotation value and Rf values upon thin-layer chromatography of Z-Asp(OBzl)-Asp(OBzl)-OH were quite similar to those of Z-Asp(OBzl)-OH. 相似文献
3.
YUJI NISHIUCHI MASAYUKI NAKAO MAKOTO NAKATA TERUTOSHI KIMURA SHUMPEI SAKAKIBARA 《Chemical biology & drug design》1993,42(6):533-538
γ-Carboxyglutamic acid (Gla) derivatives having several protecting groups at the γ-carboxyl function were synthesized and examined for their stabilities and removabilities under the conditions used in peptide synthesis by the Boc strategy. Among them, the cyclohexyl (cHx) group of the Gla residue was found to be stable during the synthesis of the protected peptides, but was quantitatively cleaved by the final HF treatment without decarboxylation. Using Boc-Gla(OcHx)2-OH as a starting material, the synthesis of Gla-containing peptides was achieved by the Boc strategy using a standard HF procedure for the final deprotection. 相似文献
4.
The synthesis is of Tyr(P)-containing peptides by the use of Fmoc-Tyr(PO3Me2)-OH in Fmoc/solid phase synthesis is complicated since, firstly, piperidine causes cleavage of the methyl group from the -Tyr(PO3 Me2)-residue during peptide synthesis and, secondly, harsh conditions are needed for its final cleavage. A very simple method for the synthesis of Tyr(P)-containing peptides using t-butyl phosphate protection is described. The protected phosphotyrosine derivative, Fmoc-Tyr(PO3tBu2)-OH was prepared in high yield from Fmoc-Tyr-OH by a one-step procedure which employed di-t-butyl N,N-diethyl-phosphoramidite as the phosphorylation reagent. The use of this derivative in Fmoc/solid phase peptide synthesis is demonstrated by the preparation of the Tyr(P)-containing peptides, Ala-Glu-Tyr(P)-Ser-Ala and Ser-Ser-Ser-Tyr(P)-Tyr(P). 相似文献
5.
JOHN W. PERICH MARIA RUZZENE LORENZO A. PINNA ERIC C. REYNOLDS 《Chemical biology & drug design》1994,43(1):39-46
A general synthetic method for the efficient preparation of Tyr(P) -containing peptides is described by the use of Fmoc-Tyr(PO31Bu2) -OH in Fmoc/solid-phase synthesis followed by simultaneous cleavage of the peptide from the resin and peptide deprotection by acidolytic treatment. The applicability of this approach is demonstrated by the synthesis of H-Ser-Ser-Ser-Tyr(P) -Tyr(P) -OH.TFA and the synthesis of the phosphorylated forms of the two physiological peptides, angiotensin II and neurotensin 8–13. In addition, the three phosphorylated peptides were used as substrates in the study of the local specificity determinants of T-cell protein tyrosine phosphatase. In a competition assay using 32P-radiolabeled [Tyr(P)]4-angiotensin II, both un-labeled synthetic [Tyr(P)]4-angiotensin II and Ser-Ser-Ser-Tyr(P) -Tyr(P) reduced the release of 32P and indicated that they efficiently competed as substrates for the phosphatase. Conversely, [Tyr(P)]4-neurotensin 8–13 was ineffective as a competitive substrate and indicated that this particular Tyr(P) -containing peptide sequence was not recognized by the enzyme. The marked difference in the recognition of Asp-Arg-Val-Tyr(P) -Ile-His-Pro-Phe and Arg-Arg-Pro-Tyr(P) -Ile-Leu is consistent with the presence of an acidic residue in the -3 position relative to the Tyr(P) residue. 相似文献
6.
DONALD YAMASHIRO RAFFAELLA GARZIA R. GLENN HAMMONDS CHOH HAO LI 《Chemical biology & drug design》1982,19(3):284-289
Four analogs of human β-endorphin (βh-EP) were synthesized by the solid-phase method: βh-EP-(1–9) (I), [D-Ala2]-βh-EP-(1–9) (II), [Gln8]-βh-EP-(1–9) (III), and [D-Ala2, Gln8]-βh-EP-(1–9) (IV). Measurement in a radioreceptor binding assay with use of tritiated βh-EP as primary ligand gave relative potencies as follows: Met-enkephalin, 100; I, 76; II, 100; III, 200; IV, 200. Two new amino acid derivatives were prepared and used for synthesis of the analogs: Nα-t-butyloxycarbonyl-O-(cyclopentyl) -tyrosine and Nα-t-butyloxycarbonyl-γ-(cyclopentyl)-glutamic acid. 相似文献
7.
The multiple Ser(P)-containing peptides, H-Ser(P)-Ser(P)-Ser(P)-Glu-Glu-NHMe-TFA, H-Asp-Ser(P)-Ser(P)-Glu-Glu-NHMe-TFA and H-Glu-Ser(P)-Ser(P)-Glu-Glu-NHMe-TFA were prepared by the use of Boc-Ser(PO3Ph2)-OH in the Boc mode of solution phase peptide synthesis followed by platinum-mediated hydrogenolytic de-protection of the Ser(PO3Ph2)-containing peptides. The protected peptides were assembled using the mixed anhydride coupling methods with 40% TFA/CH2C12 used for removal of the Boc group from intermediate Boc-protected peptides. 相似文献
8.
JOHN W. PERICH DAVID P. KELLY And ERIC C. REYNOLDS 《Chemical biology & drug design》1993,41(3):275-281
The protected phosphothreonine derivative Boc-Thr(PO3Ph2)-OH was prepared in high yield from Boc-Thr-OH by a simple three-step procedure which involved 4-nitrobenzylcarboxyl protection, either phosphorotriester (diphenyl phosphorochloridate) or “phosphite-triester” (diphenyl N.N-diethylphosphoramidite) phosphorylation of the thrconine hydroxyl group of Boc-Thr-ONb followed by hydrogenolytic carboxyl deprotection. The three Thr(P)-containing peptides, H-Thr(P)-Glu-Glu-NHMe.TFA, H-Thr(P)-Thr(P)-Glu-Glu-NHMe.TFA and H-Thr(P)-Thr(P)-Thr(P)-Glu-Glu-NHMe.TFA, were prepared in high yield by the use of Boc-Thr(PO3Ph2)-OH in the Boc mode of peptide synthesis (mixed anhydride method) followed by platinum-mediated hydrogenolytic deprotection of the Thr(PO33Ph2)-containing peptides. The use of the phosphopeptides in calcium phosphate binding studies showed that the triple Thr(P)-cluster was a basic structural requirement, since only the pentapeptide was able to bind calcium phosphate efficiently. 相似文献
9.
BRIAN M. PEEK GLENN T. ROSS STEPHEN W. EDWARDS GERALD J. MEYER THOMAS J. MEYER BRUCE W. ERICKSON 《Chemical biology & drug design》1991,38(2):114-123
Boc-l -Lysine derivatives and lysine-containing peptides bearing the electron donor 10H-phenothiazine (PTZ) or the redox chromophore tris(2,2′-bipyridine)ruthenium(II) dication ([Rub3,]2H, where b is 2,2-bipyridine) have been synthesized and characterized. SeO2 oxidation (53% yield) of 4,4′-dimethyl-2,2′-bipyridine, Ag2:O oxidation (85% yield) of the monoaldehyde, complexation (96% yield) of 4′-methyl-2,2′-bipyridine-4-carboxylic acid (m-OH) with Rub2Cl2:. activation (81% yield) of the acid [Rub2m-OH]2+ (PF6?)2, and condensation (83% yield) of the succinimido ester [Rub2m-OSu]2+ (PF6?)2 with Boc-Lys furnished the protected redox-chromophore module [Boc-Lys(Rub2m)-OH]2+(PF6?)2 in 29% overall yield over five steps. The first two steps constitute the first practical synthesis of the monocarboxylic acid m-OH (45% overall yield). Also prepared were m-OSu, Boc-Lys(m)-OH, Boc-Lys(m)-OCH3, and [Rub2m-NHCH3]2+ (PF6?)2:. Activation (91% yield) of 3-(10H-phenothiazine-10)propanoic acid (PTZpn-OH) and condensation (92% yield) of the succinimido ester PTZpn-OSu with Boc-Lys furnished the protected electron-donor module Boc-Lys(PTZpn)-OH (84% overall yield). The latter was used in solid-phase syntheses of two redox tripeptides. CH3CO-Ala-Lys(PTZpn)-Ala-OH and [Rub2m-Ala-Lys(PTZpn)-Ala-OH]2 (PF6?)2. The electrochemical properties of these redox amino acids and peptides were similar to those of PTZpn-OH, [Rub2 m-OH]2+(PF6)2. or [Rub2 m-NHCH3]2+ (PF6?)2. Lys(PTZpn). [Lys(Rub2m)]2+ (PF6)2:. and other redox modules may be useful for engineering light-harvesting proteins, photovoltaic cells, and other molecular electronic devices. 相似文献
10.
ALEXIOS ALETRAS KLEOMENIS BARLOS DIMITRIOS GATOS SOPHIA KOUTSOGIANNI PETROS MAMOS 《Chemical biology & drug design》1995,45(5):488-496
N α-9-Fluorenylmethoxycarbonyl-Nε-4-methyltrityl-lysine, [Fmoc-Lys(Mtt)-OH], was prepared in two steps from lysine, in 42% overall yield. The Nε-Mtt function can be quantitatively removed upon treatment with 1% TFA in dichloromethane or with a 1:2:7 mixture of acetic acid/trifluoroethanol/dichloromethane for 30 min and 1 h at room temperature, respectively. Under these conditions, groups of the tert-butyl type and peptide ester bonds to TFA-labile resins, such as the 2-chlorodiphenylmethyl- and the Wang-resin, remained intact. The utility of the new derivative in peptide synthesis has been exemplified with the synthesis of a cyclic cholecystokinin analog. As an example of further application, five types of lysine cores suitable for the solid-phase synthesis of one, two or three epitopes containing antigenic peptides or template-assembled synthetic proteins have been synthesized on Merrifield, Wang and 2-chlorodiphenylmethyl resin. © Munksgaard 1995. 相似文献
11.
Rinku Baishya Dipak K. Nayak Nabanita Chatterjee Kamal K. Halder Sanmoy Karmakar Mita C. Debnath 《Chemical biology & drug design》2014,83(1):58-70
During the past decade, several peptides containing Arg‐Gly‐Asp sequence have been conjugated with different chelating agents for labeling with various radionuclides for the diagnosis of tumor development. In this study, we report the synthesis of two tetrapeptides (Asp‐Gly‐Arg‐His and Asp‐Gly‐Arg‐Cys) and one hexapeptide [Asp‐Gly‐Arg‐D‐Tyr‐Lys‐His] by changing the amino acid sequence of the Arg‐Gly‐Asp motif. Peptide synthesis was initiated from aspartic acid. Aspartic acid placed at C‐terminal end of the peptide chain can be conjugated with different drug molecules facilitating their transport to the site of action. The peptides were synthesized in excellent yield and labeled using freshly prepared [99mTc(CO)3(H2O)3]+ intermediate. A complexation yield of over 97% was achieved under mild conditions even at low ligand concentrations of 10?2 m . Radiolabeled peptides were characterized by HPLC and were found to be substantially stable in saline, in His solution as well as in rat serum and tissue (kidney, liver) homogenates. Internalization studies using Ehrlich ascites carcinoma cell line showed rapid and significant internalization (30–35% at 30 min of incubation attaining maximum value of about 40–60% after 2–4 h incubation). A good percentage of quick internalization was also observed in αvβ3‐receptor‐positive B16F10 mouse melanoma cell line (14–16% after 30 min of incubation and 25–30% after 2–4 h incubation). Imaging and biodistribution studies were performed in Swiss albino mice bearing Ehrlich ascites tumor in right thigh. Radiolabeled peptides exhibited fast blood clearance and rapid elimination through the urinary systems. 99mTc(CO)3‐tetra‐Pep2 exhibited remarkable localization at tumor site (1.15%, 1.17%, and 1.37% ID/g at 2, 4, and 6 h p.i., respectively) which could be due to slow clearance of the radiolabeled peptide from blood in comparison with the other two radiolabeled peptides. However, 99mTc(CO)3‐hexa‐Pep exhibited the highest tumor to muscle and tumor to blood ratios among the three. The preliminary results with these amino acid–based peptides are encouraging enough to carry out further experiments for targeting tumor. 相似文献
12.
Previous work has reported that the 5-hydroxytryptamine (5-HT)1A agonist, 8-hydroxy 2-(di-n-propylamino)tetralin (8-OH DPAT), reduces ethanol intake by rats. However, as 8-OH DPAT reduces 5-HT neurotransmission, these findings are inconsistent with the proposed inhibitory role of central 5-HT neurons on ethanol intake. We examined the effect of 8-OH DPAT on ethanol, water and food intake in rats maintained on a limited access schedule using a lower dose range (6–250 µg/kg) and by assessing concomitant changes in behaviour. Low doses of 8-OH DPAT enhanced ethanol intake even when food and water were offered as alternatives. Suppression in ethanol intake was observed at higher doses where elements of the 5-HT syndrome were apparent. Similar observations were made in both fluid and non-fluid deprived water drinking rats, suggesting the latter effect is non-selective. Therefore 8-OH DPAT may both increase or decrease ethanol consumption in the rat depending on the dose used. 相似文献
13.
ALENKA PAQUET BARBARA BLACKWELL MICHAEL JOHNS JOHN NIKIFORUK 《Chemical biology & drug design》1997,50(4):262-268
Suitability of bis-(2, 2, 2-trichloro)ethyl (Tc) groups for protection of phosphate moiety in Boc-mode synthesis of phosphotyrosine peptides is demonstrated Boc-Tyr(PO3 Tc2)-OH and Fmoc-Tyr(PO3Tc2)-OH were prepared by acylating H-Tyr(PO3Tc2)-OH with (Boc)2O and Fmoc-ONSu, respectively. Phosphorus introduction was achieved by phosphorylating Boc-Tyr-OBzl with Tc phosphochloride. The Tc-phosphorus protector was found to be incompatible with the Fmoc group because the conditions of Fmoc removal (piperidine treatment) caused dephosphorylation. Complete NMR spectral assignments in the described compounds is presented. (Contribution No. 2398 from the Centre for Food and Animal Research). 相似文献
14.
JOHN W. PERICH EVELYNE TERZI ERIC CARNAZZI RENE SEYER ELISABETH TRIFILIEFF 《Chemical biology & drug design》1994,44(4):305-312
The Ser(P)-containing peptide corresponding to phospholamban 11-19, Ac-Ala-Ile-Arg-Are-Ala-Ser(P)-Thr-Ile-Glu-NH2, was prepared by the use of Boc-Ser(PO3Ph2)-OH in Boc/solid-phase peptide synthesis followed by HF cleavage of the peptide from the polystyrene resin and subsequent platinum-mediated hydrogenolytic cleavage of the phenyl phosphate groups. A study of the HF deprotection step showed that extensive dephosphorylation of the Ser(PO3Ph2)-residue occurred using three commonly used HF conditions and gave rise to large quantities of the Ser-containing peptide. The subsequent study of model peptide systems under standard HF conditions established firstly that the extent of dephosphorylation was dependent on the HF-contact time, and secondly that the Ser(PO3Ph2) residue underwent dephosphorylation at a slightly higher rate than the Thr(PO3Ph2) residue. © Munksgaard 1994. 相似文献
15.
The solution syntheses of cyclo-(Xxx-Pro-D-Gln)2, where Xxx=Gly, Ala, Leu, Phe and Val are described. Several routes were examined, the most successful involving the intermediate Z-Xxx-Pro-D-Gln-O-tBu and proceeding to cyclization of H-Xxx-Pro-D-Gln-Xxx-Pro-D-Gln-OH using diphenylphosphoryl azide. The N-H regions of the proton magnetic resonance spectra of aqueous solutions of these peptides were examined, and in the Xxx=Leu and Val peptides an unsymmetrical backbone, presumably with one cis Xxx-Pro peptide bond, was found to be important. Previous reports of cyclo-(Xxx-Pro-D-Yyy)2 peptides have shown only C2-symmetric forms. 相似文献
16.
Two cyclic tripeptide homologs, cyclo(Glu[Cys-β-Ala-]-OH) 8a, and cyclo(Glu[Cys-Gaba-]-OH) 8b, were synthesized by the pentafluorophenyl ester method in solution (1-3). These cyclic peptides are cyclo homologs of glutathione and are designed as potential antitumor agents. The 1H- and 13C-n.m.r. spectral parameters of cyclo(Glu[Cys(Bzl)-β-Ala-]-OH) 7a were measured in DMSO-d6 and a possible conformation has been proposed. The cyclic peptide 8a showed low cytotoxic activities against three human tumor cell lines: KB, HeLa, and Colo 205. 相似文献
17.
ALENKA PAQUET 《Chemical biology & drug design》1992,39(1):82-86
Boc-Ser(PO3Tc2)-OH, Z-Ser(PO3Tc2)-OH and Fmoc-Ser(PO3Tc2)-OH, derivatives useful for peptide synthesis, have been obtained in high yields by acylation of H-Ser(PO3Tc2)-OHCF3COOH. The latter was obtained from Boc- or Z-Ser(PO3Tc2)-OBzl by simultaneous removal of the amino- and carboxy-protecting groups by Pd-catalyzed hydrogenolysis in acetic acid-trifiuoroacetic acid solution. Removal of the Tc-protecting group was efficiently achieved by hydrogenolysis in aqueous ethanol. 相似文献
18.
KLEOMENIS BARLOS DIMITRIOS GATOS STAVROS KAPOLOS CONSTANTINE POULOS WOLFRAM SCHFER YAO WENQING 《Chemical biology & drug design》1991,38(6):555-561
The carboxyl terminal dipeptide amide, Fmoc-Asp-Phe-NH2, of gastrin and cholecystokinin (CCK) has been attached in high yield through its free side chain carboxyl group to the acid labile 2-chlorotrityl resin. The obtained peptide resin ester has been applied in the solid phase synthesis of partially protected (Leu15)-gastrin I utilising Fmoc-amino acids. Quantitative cleavage of this peptide from resin, with the t-butyl type side chain protection intact is achieved using mixtures of acetic acid/trifluoroethanol/dichloro-methane. Under the same conditions complete detritylation of the tyrosine phenoxy function occurs simultaneously. Thus, the solid-phase synthesis of peptides selectively deprotected at the side chain of tyrosine is rendered possible by the use of 2-chlorotrityl resin and Fmoc-Tyr(Trt)-OH. The efficiency of this approach has been proved by the subsequent high-yield synthesis of three model peptides and the CCK-octapeptide. 相似文献
19.
The chemistry associated with the process of N,O-acyl migration was explored in both cyclic and linear peptides under aqueous acid conditions. The importance of backbone cyclization and N-methylation of the peptide bond on the kinetics of N,O-acyl migration in a series of linear and cyclic peptides related in structure to cyclosporin A (CsA) were examined. The similarity in the chemical reactivity of the cyclic peptide [MeLeu (3-OH)]1-CsA and the corresponding linear peptide [Val-MeLeu (3-OH)-Abu], suggested that for this series, cyclization of the peptide backbone may not play an important role in controlling the kinetics of N,O-acyl migration. In contrast, the disparity in the chemical reactivity of tripeptides [Val-MeLeu (3-OH)-Abu] and [Val-Leu (3-OH)-Abu], indicated that N-methylation of amide bond significantly impacted the kinetics. Various hypothesis are proposed to account for this observation. 相似文献
20.
D.S. KEMP NADER FOTOUHI JAMES G. BOYD ROBERT I. CAREY CHRISTOPHER ASHTON JOHN HOARE 《Chemical biology & drug design》1988,31(4):359-372
Reproducible preparations are given for salts of the following L-amino acid derivatives: Bpoc-Ala-OH, Bpoc-Arg(Mtr)-OH, Bpoc-Asn-OH, Bpoc-Asp(OtBu)-OH, Bpoc-Cys(Acm)-OH, Bpoc-Cys(S-tBu)-OH, Bpoc-Gln-OH, Bpoc-Glu(OtBu)-OH, Bpoc-Gly-OH, Bpoc-Ile-OH, Bpoc-Leu-OH, N-α-Bpoc-Lys(ε-Boc)-OH, Bpoc-Met-OH, Bpoc-Phe-OH, Bpoc-Pro-OH, Bpoc-Ser(OtBu)-OH, Bpoc-Thr(OtBu)-OH, Bpoc-Tyr-OH, Bpoc-Val-OH. A study of the deblocking of N-α-Bpoc peptides in dichloromethane containing 0.5% trifluoroacetic acid revealed that a rapid equilb-rium is established between the first-formed monomeric alkene 2-p-biphenylylpropene and the hindered dimer 2,4-bis(p-biphenylyl)-4-methyl-l-pentene. Thioethers were found to be inefficient carbocation scavengers for the deblocking reaction. The most efficient scavengers were found to be thiophenol and benzyl mercaptan, and the following approximate reactivity order was established: benzyl mercaptan ~ thiophenol 〉 indole 1,3-dimethoxybenzene ~ resorcinol 〉1,3,5-trimethoxybenzene ~ dimethyl sulfide ~ thioanisole. 相似文献