Peptides that mimic glycosaminoglycans: high-affinity ligands for a hyaluronan binding domain.

BACKGROUND: Hyaluronan (HA) is a non-sulfated glycosaminoglycan (GAG) that promotes motility, adhesion, and proliferation in mammalian cells, as mediated by cell-surface HA receptors. We sought to identify non-carbohydrate ligands that would bind to and activate cell-surface HA receptors. Such analogs could have important therapeutic uses in the treatment of cancer, wound healing, and arthritis, since such ligands would be resistant to degradation by hyaluronidase (HAse). RESULTS: Peptide ligands that bind specifically to the recombinant HA binding domain (BD) of the receptor for hyaluronan-mediated motility (RHAMM) were obtained by screening two peptide libraries: (i) random 8-mers and (ii) biased 8-mers with alternating acidic side chains, i.e. XZXZXZXZ (X=all-L-amino acids except Cys, Lys, or Arg; Z=D-Asp, L-Asp, D-Glu, or L-Glu). Selectivity of the peptide ligands for the HABD was established by (i) detection of binding of biotin- or fluorescein-labeled peptides to immobilized proteins and (ii) fluorescence polarization of FITC-labeled peptides with the HABD in solution. HA competitively displaced binding of peptides to the HABD, while other GAGs were less effective competitors. The stereochemistry of four biased octapeptides was established by synthesis of the 16 stereoisomers of each peptide. Binding assays demonstrated a strong preference for alternating D and L configurations for the acidic residues, consistent with the calculated orientation of glucuronic acid moieties of HA. CONCLUSIONS: Two classes of HAse-resistant peptide mimetics of HA were identified with high affinity, HA-compatible binding to the RHAMM HABD. This demonstrated that non-HA ligands specific to a given HA binding protein could be engineered, permitting receptor-specific targeting.     

Two new glycosides from the whole plants of Glechoma hederacea L

Two new glycosides, 7S,7'S,8R,8'R-icariol A(2)-9-O-beta-D-glucopyranoside (1) and 4-allyl-2-hydroxyphenyl 1-O-beta-D-apiosyl-(1-->6)-beta-D-glucopyranoside (2), were isolated from the dried whole plants of Glechoma hederacea L. (Labiatae) together with four known compounds, cistanoside E (3), dihydrodehydrodiconiferyl alcohol 4-O-beta-D-glucopyranoside (4), apigenin 7-O-beta-D-glucuronopyranoside (5) and luteolin 7-O-beta-D-glucopyranoside (6). The structures of the new compounds were elucidated on the basis of chemical and spectral analysis.     

Inhibitory effects of constituents from Euphorbia lunulata on differentiation of 3T3-L1 cells and nitric oxide production in RAW264.7 cells

A new flavonol galactopyranoside, myricetin 3-O-(2',3'-digalloyl)-β-D-galactopyranoide (1), and 23 known constituents, including myricetin 3-O-(2'-galloyl)-β-D-galactopyranoide (2), myricitrin (3), myricetin (4), quercetin 3-O-(2', 3'-digalloyl)-β-D-galactopyranoide (5), quercetin 3-O-(2'-galloyl)-β-D-galactopyranoide (6), hyperin (7), isoquercetrin (8), quercetin (9), kaempferol (10), apigenin (11), luteolin (12), 3-O-methylquercetin (13), 5,7,2',5'-tetrahydroxyflavone (14), 1,3,4,6-tetra-O-galloyl-β-D-glucose (15), 1,2,6-tri-O-galloyl-β-D-glucose (16), 1,3,6-tri-O-galloyl-β-D-glucose (17), gallic acid (18), protocatechuic acid (19), 3,4,5-trimethoxybenzoic acid (20), 2,6-dihydroxyacetophenone (21), 3,3'-di-O-methylellagic acid (22), ellagic acid (23) and esculetin (24) were isolated from Euphorbia lunulata Bge. Their structures were determined by spectroscopic analysis. Isolated hydrolysable tannins, flavonoids, and flavonol galactopyranoside gallates showed significant inhibition of the differentiation of 3T3-L1 preadipocytes and triglyceride accumulation in maturing adipocytes, and nitric oxide production in RAW 264.7 cells.     

Five new phenylethanoid glycosides from the whole plants of Lamium purpureum L

Five new phenylethanoid glycosides, lamiusides A (1), B (2), C (3), D (4) and E (5), were isolated from the whole plants of Lamium purpureum L. (Labiatae) together with seven known compounds (6-12). On the basis of chemical and spectral analyses, the structures of the new compounds were elucidated to be 2-(3,4-dihydroxyphenyl)ethyl-O-beta-D-galactopyranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->3)-(4-O-trans-caffeoyl)-beta-D-glucopyranoside (1), 2-(3,4-dihydroxyphenyl)ethyl-O-beta-D-galactopyranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->3)-(4-O-trans-feruloyl)-beta-D-glucopyranoside (2), 2-(3,4-dihydroxyphenyl)ethyl-O-beta-D-galactopyranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->3)-(6-O-trans-caffeoyl)-beta-D-glucopyranoside (3), 2-(3,4-dihydroxyphenyl)-R,S-methoxy-ethyl-O-beta-D-galactopyranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->3)-(4-O-trans-caffeoyl)-beta-D-glucopyranoside (4) and 2-(3-hydroxy-4-methoxyphenyl)ethyl-O-alpha-L-rhamnopyranosyl-(1-->3)-beta-D-glucopyranosyl-(1-->6)-(4-O-cis-feruloyl)-beta-D-glucopyranoside (5). In addition, the radical-scavenging activities of compounds 1-4 on 1,1-diphenyl-2-picrylhydrazyl radical were examined.     

Phenylpropenol ester and sesquiterpenoids with antimetastatic activities from the whole plants of Chloranthus japonicus

One new phenylpropenol ester (1) and three new lindenane sesquiterpenes (2–4) were isolated from the whole plant of Chloranthus japonicus together with three known lindenane derivatives (5–7). Their structures were determined based on detailed spectroscopic and electronic circular dichroism computational analyses. Compound 4 showed moderate efficacy in inhibiting cell migration, invasion, and vasculogenic mimicry (VM) in human of hepatocarcinoma (HCC) HepG2 cells. Furthermore, compound 4 could alter the expression of the proteins Vimentin, N-cadherin, Snail1 and E-cadherin by down-regulating the expression of Twist1, which indicated that its antimetastatic effect was associated with restraining the epithelial-mesenchymal transition (EMT) in HepG2 cells.     

Flavonoids of the cotton plant and plants close to it

This review gives information on the distribution of flavonoids (flavonol and anthocyanin glycosides, catechins, and proanthocyanidins in plants of the family Malvaceae, namely the various species of the genera Gossypium, Hibiscus, Altheae, etc. It is shown that the flavonols are represented by glycosides of kaempferol, quercetin, myricetin, herbacetin. gossypetin, and hibiscetin, the most widespread being glycosides of quercetin and kaempferol. Characteristic for the majority of representatives of the families that were studied are flavonols having a hydroxy group in the C-8 position. Anthocyanins are represented by glycosides of cyanidin and of delphinidin. However, together with these, glycosides of methoxylated anthocyanins have also been detected — peonidin, petinidin, and malvidin. Sources of a food dye have been revealed among representatives of the family. Literature sources up to 1991 have been included.A. S. Sadykov Institute of Bioorganic Chemistry, Academy of Sciences of the Republic of Uzbekistan, Tashkent, fax 627071. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 3–19, January–February, 1994.     

Eight New Diterpenoids from the Roots of Euphorbia nematocypha

From the dried roots of Euphorbia nematocypha, eight new diterpenoids, with ent‐atisane (i.e., 1 – 5 ) and isopimarane (i.e., 6 – 8 ) type skeletons, together with five known compounds, were isolated. The structures of these new compounds were elucidated by spectroscopic data. Compounds 1 – 8 were evaluated for their cytotoxicity against a small panel of human cancer cell lines.     

Chemical Constituents from the Whole Plant of Euphorbia altotibetic

Four new jatrophane diterpenoids, altotibetin A ( 1 ), altotibetin B ( 2 ), altotibetin C ( 3 ), altotibetin D ( 4 ), and nine known compounds, β‐sitosterol, cycloart‐23‐ene‐3β,25‐diol, cycloart‐25‐ene‐3β,24‐diol, lupeol acetate, scopoletin, kaempferol, uracil, uridine, astragalin, and daucosterol have been isolated from the whole plant of Euphorbia altotibetic Pauls . Their structures were established by spectral methods, and the configurations of 1 and 2 were confirmed by X‐ray analysis.     

A new phenylpropanoid from the roots of Euphorbia nematocypha

A phytochemical investigation of the ethanolic extracts of the dried roots of Euphorbia nematocypha resulted in the isolation of a new phenylpropanoid, 16-O-caffeoyl-16-hydroxylhexadecanoic acid (1), together with 23 known compounds (2–24). Their structures were elucidated on the basis of spectroscopic data. Compound 1 was first to be isolated as a caffeic acyl long chain alkyl acid from the family Euphorbiaceae. The new isolated phenylpropanoid showed potent cytotoxic activities against the MCF-7 and HeLa cell lines.     

大戟属三萜类结构及生物活性*

大戟属植物在全世界分布有2000多种,对于本属植物二萜类成分及生物活性的综述报道较多,但是还未见关于三萜类化学成分及生物活性的综述报道。本文综述了该属植物各种类型三萜化合物（羊毛脂烷型、环阿尔廷烷型、大戟烷型、甘遂烷型、齐敦果烷型、乌苏烷型及羽扇豆烷型等）的化学性能以及抗肿瘤、抗炎抗菌、抗病毒等主要生物活性的研究。