1080-06-4Relevant articles and documents
Clement et al.
, p. 5603 (1968)
Stabilized 111In-labeled sCCK8 analogues for targeting CCK2-receptor positive tumors: Synthesis and evaluation
Roosenburg, Susan,Laverman, Peter,Joosten, Lieke,Eek, Annemarie,Oyen, Wim J. G.,De Jong, Marion,Rutjes, Floris P. J. T.,Van Delft, Floris L.,Boerman, Otto C.
, p. 663 - 670 (2010)
Radiolabeled cholecystokinin-8 (CCK8) peptide analogues can be used for peptide receptor radionuclide imaging and therapy for tumors expressing CCK2/gastrin receptors. Earlier findings indicated that sulfated CCK8 (sCCK8, Asp-Tyr(OSO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2) may have better characteristics for peptide receptor radionuclide therapy (PRRT) than gastrin analogues. However, sCCK8 contains an easily hydrolyzable sulfated tyrosine residue and two methionine residues which are prone to oxidation. Here, we describe the synthesis of stabilized sCCK8 analogues, resistant to hydrolysis and oxidation. Hydrolytic stability was achieved by replacement of the Tyr(OSO3H) moiety by a robust isosteric sulfonate, Phe(p-CH 2SO3H). Replacement of methionine by norleucine (Nle) or homopropargylglycine (HPG) avoided undesired oxidation side-reactions. The phenylalanine analogue Phe(p-CH2SO3H) of l-tyrosine, synthesized by a modification of known synthetic routes, was incorporated in three peptides: sCCK8[Phe2(p-CH2SO3H),Met 3,6], sCCK8[Phe2(p-CH2SO3H),Nle 3,6], and sCCK8[Phe2(p-CH2SO 3H),HPG3,6]. All peptides were N-terminally conjugated with the macrocyclic chelator DOTA (1,4,7,10-tetraazacyclododecane-N,N,N,N- tetraacetic acid) and radiolabeled with In-111. In vitro binding assays on CCK2R-expressing HEK293 cells revealed that all three peptides showed specific binding and receptor-mediated internalization, with binding affinity values (IC50) in the nanomolar range. In vitro oxidation studies demonstrated that peptides with Nle or HPG indeed were resistant to oxidation. In vivo targeting studies in mice with AR42J tumors showed that tumor uptake was highest for 111In-DOTA-sCCK8 and 111In-DOTA- sCCK8[Phe2(p-CH2SO3H),Nle3,6] (4.78 ± 0.64 and 4.54 ± 1.15%ID/g, respectively, 2 h p.i.). The peptide with the methionine residues replaced by norleucine (111In-DOTA- sCCK8[Phe2(p-CH2SO3H), Nle3,6]) showed promising in vivo characteristics and will be further investigated for radionuclide imaging and therapy of CCK2R-expressing tumors.
Synthesis, characterization and in vitro antimicrobial and biodegradability study of pseudo-poly(amino acid)s derived from N,N′-(pyromellitoyl)-bis- l-tyrosine dimethyl ester as a chiral bioactive diphenolic monomer
Mallakpour, Shadpour,Tirgir, Farhang,Sabzalian, Mohammad R.
, p. 611 - 621 (2011)
In this investigation N,N′-(pyromellitoyl)-bis-l-tyrosine dimethyl ester (7) as a chiral bioactive diphenolic monomer was prepared in three steps. The aim of this work was to obtain novel optically and biologically active pseudo-poly(amino acid)s (PAA)s that are more soluble in common organic solvents while maintaining their high thermal stability. Thus, several new, highly soluble, thermally stable, optically active and biodegradable PAAs containing different amino acid moieties in the main chain were prepared with moderate molecular weights via direct polycondensation using tosyl chloride, pyridine and N,N′-dimethylformamide as a condensing agent. The resulting novel polymers were characterized with FT-IR, 1H-NMR, elemental and thermogravimetric analysis techniques. In addition, in vitro toxicity and biodegradability behavior of the diphenolic monomer 7, different synthetic diacids (3a-3e) and obtained PAAs, which were investigated in culture media, showed that the synthesized compounds and polymers derived from them are biologically active and biodegradable under a natural environment.
Fabrication of biodegradable poly(ester-amide)s based on tyrosine natural amino acid
Abdolmaleki, Amir,Mallakpour, Shadpour,Borandeh, Sedigheh,Sabzalian, Mohammad R.
, p. 1997 - 2007 (2012)
N,N'-Bis[2-(methyl-3-(4-hydroxyphenyl)propanoate)] isophthaldiamide (5), a novel diol monomer containing chiral group, was prepared by the reaction of S-tyrosine methyl ester (3) with isophthaloyl dichloride (4a). A new family of optically active and potentially biodegradable poly(ester-amide)s (PEAs) based on tyrosine amino acid were prepared by the polycondensation reaction of diol monomer 5 with several aromatic diacid chlorides. The resulting new polymers were obtained in good yields with inherent viscosities ranging between 0.25 and 0.42 dL/g and are soluble in polar aprotic solvents. They showed good thermal stability and high optical purity. The synthetic compounds were characterized and studied by FT-IR, 1H-NMR, specific rotation, elemental and thermogravimetric analysis (TGA) techniques and typical ones by 13C-NMR, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and field emission scanning electron microscopy (FE-SEM) analysis. Soil burial test of the diphenolic monomer 5, and obtained PEA6a, and soil enzymatic assay showed that the synthesized diol and its polymer are biologically active and probably biodegradable in soil environment. Springer-Verlag 2011.
Differentiation of natural and synthetic phenylalanine and tyrosine through natural abundance 2H nuclear magnetic resonance
Brenna, Elisabetta,Fronza, Giovanni,Fuganti, Claudio,Pinciroli, Matteo
, p. 4866 - 4872 (2003)
The natural abundance deuterium NMR characterization of samples of the amino acids tyrosine (1) and phenylalanine (2), examined as the acetylated methyl esters 4 and 6, has been performed with the aim to identify by these means the contribution in animals of the hydroxylation of the diet L-phenylalanine (2) to the formation of L-tyrosine (1), a feature previously revealed on the same samples through the determination of the phenolic δ18O values. The study, which includes also the NMR examination of benzoic acid (5) from 2 and of tyrosol (7) from 1, substantially fails in providing the required information because the mode of deuterium labeling of tyrosine samples of different origins is quite similar but indicates a dramatic difference in the deuterium labeling pattern of the two amino acids 1 and 2. The most relevant variation is with regard to the deuterium enrichments at the CH2 and CH positions, which are inverted in the two amino acids of natural derivation. Moreover, whereas the diastereotopic benzylic hydrogen atoms of L-tyrosine (1) appear to be equally deuterium enriched, in L-phenylalanine (2) the (D/H)3R > (D/H)3S. Similarly, benzoic acid (5) shows separate signals for the aromatic deuterium nuclei, which are quite indicative of the natural or synthetic derivation. The mode of deuterium labeling of the side chain of 1 and 2 is tentatively correlated to the different origins of the two amino acids, natural from animal sources for L-tyrosine and biotechnological probably from genetically modified microorganisms for L-phenylalanine.
Synthesis of d,l-amino acid derivatives bearing a thiol at the β-position and their enzymatic optical resolution
Morishita, Yasuhito,Kaino, Tomoka,Okamoto, Ryo,Izumi, Masayuki,Kajihara, Yasuhiro
, p. 6565 - 6568 (2015)
Amino acids bearing a thiol group at the β-position are useful for native chemical ligation. Phenylalanine and tyrosine derivatives bearing a thiol group at the β-position were synthesized. Racemic phenylalanine and tyrosine were selected as starting materials and were introduced a bromo atom at the β-position by photoreaction. Subsequent substitution reaction of the bromo atom with p-methoxybenzylmercaptan yielded the corresponding amino acids bearing a thiol group at the β-position. Enzymatic optical resolution using l-aminoacylase and subsequent chemical conversion gave the corresponding optically pure l- and d-phenylalanine and tyrosine derivatives bearing a thiol group at the β-position.
Enantioselective Aza-Diels Alder reaction catalyzed by clay supported Schiff base complex?
Kannan,Sreekumar
, p. 153 - 160 (2021)
Clay supported catalysts based on 2- hydroxy naphthaldehyde and amino acids, their copper and titanium complexes have been described. The catalysts were found to be active toward the synthesis of pyrano-, furanoquinolines through Aza-Diels Alder reaction. The catalysts gave good yield and high enantioselectivity. The catalysts were environmentally friendly, economical, synthetically robust and reusable.
L-O-(2-malonyl)tyrosine (L-OMT) a new phosphotyrosyl mimic suitably protected for solidphase synthesis of signal transduction inhibitory peptides
Ye, Bin
, p. 4733 - 4736 (1995)
A new phosphotyrosyl (pTyr) mimic L-O-(2-malonyl)tyrosine (L-OMT, 4) utilizes a malonyl structure in place of the parent phosphate group. This compound is stable to protein-tyrosine phosphatases and has advantages over phosphonate-based pTyr mimics in that protection of the malonyl group as its diester allows passage of the OMT across cell membranes, with subsequent esterase-mediated liberation of the free diacid once inside cells. Herein is reported the synthesis of Nα-Fmoc-L-OMT-O,O-(ferf-butyl)2 (5) for the solid-phase synthesis of L-OMT containing peptides as modulators of cellular signal transduction. Additionally included is the preparation of Nα-Fmoc-L-OMT-O,O-(n-butyl)2 (6) for the direct solid-phase synthesis of OMT-peptide diester prodrugs for use in cell-based studies.
Palladium-catalyzed oxalyl amide assisted direct ortho-alkynylation of arylalkylamine derivatives at δ and ε positions
Guan, Mingyu,Chen, Changpeng,Zhang, Jingyu,Zeng, Runsheng,Zhao, Yingsheng
, p. 12103 - 12106 (2015)
Palladium-catalyzed oxalyl amide directed ortho-alkynylation of arylalkylamine derivatives is reported for the first time. A wide variety of β-arylethamine and γ-arylpropamine derivatives are compatible with this protocol. This method provides a general means to synthesize substituted alkynylarylalkylamine derivatives, highlighting the ability of oxalyl amide in promoting C-H functionalization at unique δ and ε positions.
12-Hydroxy stearic acid appended new amphiphilic scaffolds for selective capture of hydrogen halides through supramolecular hydrogelation
Sharma, Ankita,Gupta, Arindam,Tiwari, Priyanka,Basu, Anindya,Duttkonar, Anita
, p. 3828 - 3832 (2020)
12-Hydroxystearic acid (12-HSA) appended new amphiphilic scaffolds reveal excellent hydrogelation propensity in the presence of aqueous acids and vapors of HCl/HBr. This selective entrapment efficiency towards hydrogen halides demonstrates an unprecedented route for the successful removal of toxic chemicals, thus providing a safe and easy protocol for environment management. We anticipate that the halide derivative of the amphiphile plays a vital role in driving the self-assembly mechanism and eventually the hydrogelation phenomena.
A small molecule peptidomimetic of spider silk and webs
Maji, Krishnendu,Sarkar, Rajib,Bera, Santu,Haldar, Debasish
, p. 12749 - 12752 (2014)
A peptidomimetic compound containing leucine, tyrosine and malonic acid self-assembles through various noncovalent interactions to form spider silk-like fibers at ambient temperature. From the high-density liquid, a liquid-solid phase transition is initiated at 20 °C and solidification occurs upon contact with air. The fiber has comprehensive mechanical strength and optical properties similar to spider silk, and can be used to mimic a natural spider web. This journal is
(4S)-p-hydroxybenzyl-1,3-oxazolidin-2-one as a solid-supported chiral auxiliary in asymmetric 1,3-dipolar cycloadditions
Faita, Giuseppe,Paio, Alfredo,Quadrelli, Paolo,Rancati, Fabio,Seneci, Pierfausto
, p. 1265 - 1269 (2000)
Evans' chiral auxiliary was grafted onto both Merrifield and Wang resins and, after functionalisation, they were used as chiral dipolarophiles in a 1,3-dipolar cycloaddition involving both a nitrile oxide and a nitrone. The cycloadducts were cleaved and analysed by chiral HPLC: the recovered supported chiral oxazolidinone was functionalised and reused in further cycloadditions. The stereochemical results as well as the possibility of recycling the chiral linker supports the applicability of solid-supported chiral auxiliaries. (C) 2000 Elsevier Science Ltd.
Synthesis of amphiphilic meso -tetrasubstituted porphyrin-L-amino acid and -heterocyclic conjugates based on m -THPP
Sweed, Ayman M. K.,Senge, Mathias O.,Atta, Sanaa M. Sh.,Farrag, Dalia S.,Abdel-Rahman, Abdel-Rahman H.,Shaker, Yasser M.
, p. 997 - 1009 (2018)
Two series of amphiphilic meso-tetrasubstituted porphyrin conjugates based on 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (m-THPP) covalently linked to L-amino acids and heterocycles were synthesized efficiently in the context of a program targeting new photosensitizers for PDT. 5,10,15-Tris(3-hydroxyphenyl)-20-(3-oxyacetic acid)phenyl]porphyrin and the respective trihexyl ether derivatives were conjugated with polar and non-polar natural L-amino acids such as glycine, L-proline, and L-tyrosine via an amide bond linker using N,N,N′,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uroniumhexafluorophosphate in diisopropylethylamine (HBTU/DIPEA). m-THPP was also conjugated with heterocyclic systems such as indole 3-acetic acid, 4-methylthiazole-5-carboxylic acid, and thiophene-2-carboxylic acid via ester linker using N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride in N-hydroxysuccinamide or 1-hydroxybenzotriazole (EDCI, NHS or HOBt). The members of the two series were obtained in good yields and characterized by UV-vis, HRMS MALDI-TOF, 1H NMR and 13C NMR spectroscopy.
Gas-phase enantioselectivity of chiral amido[4]resorcinarene receptors
Botta, Bruno,Caporuscio, Fabiana,D'Acquarica, Ilaria,Delle Monache, Giuliano,Subissati, Deborah,Tafi, Andrea,Botta, Maurizio,Filippi, Antonello,Speranza, Maurizio
, p. 8096 - 8105 (2006)
Diastereomeric proton-bound [1LHA]+ complexes between selected amino acids (A = phenylglycine (Phg), tryptophan (Trp), tyrosine methyl ester (TyrOMe), threonine (Thr), and allothreonine (AThr)) and a chiral amido[4]resorcinarene receptor (1L) display a significant enantioselectivity when undergoing loss of the amino acid guest A by way of the enantiomers of 2-aminobutanes (B) in the gas phase. The enantioselectivity of the B-to-A displacement is ascribed to a combination of thermodynamic and kinetic factors related to the structure and the stability of the diastereomeric [1LHA]+ complexes and of the reaction transition states. The results of the present and previous studies allow classification of the [1LHA]+ complexes in three main categories wherein: i) guest A does not present any additional functionalities besides the amino acid one (alanine (Ala), Phg, and phenylalanine (Phe)) ; ii) guest A presents an additional alcohol function (serine (Ser), Thr, and AThr); and iii) guest A contains several additional functionalities on its aromatic ring (tyrosine (Tyr), TyrOMe, Trp, and 3,4-dihydroxyphenylalanine (DOPA)). Each category exhibits a specific enantioselectivity depending upon the predominant [1 LHA]+ structures and the orientation of the 2-aminobutane reactant in the relevant adducts observed. The results may contribute to the understanding of the exceptional selectivity and catalytic properties of enzyme mimics towards unsolvated biomolecules.
Synthesis and Bioactivity of a Macrocidin B Stereoisomer
Weber, Stefanie E.,Ga?, Juliane,Zeng, Haoxuan,Erb-Brinkmann, Maike,Schobert, Rainer
supporting information, p. 8273 - 8276 (2021/10/25)
A stereoisomer of macrocidin B, a presumed metabolite of the fungus Phoma macrostoma, was synthesized in 18 steps and 2.7% yield from protected l-tyrosine that was N-β-ketoacylated with a fully functionalized octanoyl Meldrum's acid. Dieckmann condensation gave a 3-acyltetramic acid, which was macrocyclized via Williamson etherification between the phenol and epi-bromohydrin termini. This macrocidin B stereoisomer showed a weaker herbicidal effect than macrocidin A and no similar inhibitory effect on biofilms of Staphylococcus aureus.
