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Research was conducted to examine chalcogen atom effects on the rates of hydrolysis of chalcogenopyrylium dyes. Results indicate that the qualitative ordering of the rates can be rationalized in terms of higher stability of the thiopyrylium ring relative to the selenopyrylium ring. Findings also show that the decreasing electronegativity of the chalcogen atoms as size increases would tend to stabilize the cationic charge inductively, predicting the opposite trend in stability.

The products of the hydrolysis of chalcogenopyrylium dyes at alkaline pH under both anaerobic and aerobic conditions were analyzed. The types of hydrolysis products observed were found strongly dependent on the identity of the chalcogen atoms in the pi-framework and on the presence of molecular oxygen during the hydrolysis. It was found that chalcogenopyranomes produce modest yields in aerobic reactions.

Heteroatom scrambling occurs due to the formation of unsymmetrical tris(chalcogenopyramylmethylidene)methanes during the synthesis of unsymmetrical chalcogenopyrylium dyes. The complete chalcogenopyranyl ring is involved during heteroatom scrambling and Reverse aldol reaction with dyes has no significant influence on scrambling mechanism. Dyes have found various applications in optical recording, electrophotography and thermal dye transfer. The experimental procedure for the synthesis of unsymmetrical dyes and tris(chalcogenopyramylmethylidene)methanes is discussed.

A series of substituted N-(3,5-dichlorobenzenesulfonyl)-l-prolyl- and α-methyl-l-prolyl-phenylalanine derivatives was prepared as VLA-4/VCAM antagonists. The compounds showed excellent potency with a wide variety of neutral, polar, electron withdrawing or donating groups on the phenylalanine ring (IC50∼1 nM). Heteroaryl ring substitution for phenylalanine was also well tolerated. Pharmacokinetic studies in rat were performed on a representative set of compounds in both series. [Copyright &y& Elsevier]

Discusses the genus Polysiphonia (Rhodophyta, Ceramiales) from Santa Catalina Island, California. Characteristerics of the genus Polysiphonia; Taxonomy; Key to Tetrasiphonous species of Polysiphonia.

Energy dispersive X-ray fluorescence spectroscopy of thin sections of Laurencia snyderae Dawson shows bromine is concentrated in a cytoplasmic vesicle, the corps en cerise, a previously described structure characteristic of this genus. The presence of the brominated natural product β-snyderol is shown to be related to the presence of corps encerise in cortical cells. The presence of halogenated sesquiterpenoids in the corps en cerise of various Laurencia species is inferred from these data. [ABSTRACT FROM AUTHOR]

The ultrastructure and histochemistry of the refractile, vesiculate cells ("blasenzellen," "cellules secretrices," "gland cells") of Antithamnion defectum Kylin were examined. The refringent vacuolar contents disclosed two components of differing density: an electron opaque, proteinaceous matrix material surrounding cores of irregularly shaped, less opaque material. The cores contain less protein and more unknown material than the matrix. Part or all of the vacuolar material is synthesized by abundant rought endoplasmic reticulum (ER) and deposited in smooth surfaced cisternae that swell to form vesicles. Mitochondria are usually associated with stacks of the swelling cisternae. The vesicles enlarge by continued deposition of synthesized material and coalescence with other vesicles. All vesicles eventually coalesce to form the mature vacuole. A crystalline array of fibrils develops in the cytoplasm during later stages of vacuole enlargement. The crystal contains a sulfated, acidic polysaccharidic material. The chloroplasts, if presnet, and nucleus degenerate at vacuole maturity. Active release of the vacuolar material does not occur, and organelles for extracellular secretion are not present. Structural evidence suggests a storage, rather than secretary, function for the cells. [ABSTRACT FROM AUTHOR]

The ultrastructure and histochemistry of developing and mature cell inclusions in vegetative cells of Antithamnion defectum Kylin were examined. Those studied were chloroplast inclusions, cytoplasmic crystals and spherical bodies within the vacuole. Chloroplasts of mature vegetative cells contain an interthylakoidal, apparently noncrystalline deposit of undertermined chemical identity. The bodies are parallel to the long axis of the plastid, are square (0.13 μm) in cross-section, and up to 3 μm long. Spherical vacuolar bodies (0.5-1.5 μm diam) are formed during early stages of vacuole formation by accumulation of protein deposits in swelling endoplasmic reticulum (ER) cisternae. Swelling of smooth ER continuous to the ER containing the deposits results in the vacuole enclosing the spherical bodies. In mature cells, vesicles appear to be secreted into the preformed vacuole. Cytoplasmic proteinaceous crystalloids develop without a bounding membrane and may serve as protein reserves. [ABSTRACT FROM AUTHOR]

Acylated β-amino acids are described as potent, specific and orally bioavailable antagonists of VLA-4. The initial lead was identified from a combinatorial library. Subsequent optimization using a traditional medicinal chemistry approach led to significant improvement in potency (up to 8-fold) while maintaining good pharmacokinetic properties. [Copyright &y& Elsevier]

An alpha4beta1/alpha4beta7 dual antagonist, 35S-compound 1, was used as a model ligand to study the effect of divalent cations on the activation state and ligand binding properties of alpha4 integrins. In the presence of 1 mM each Ca2+/Mg2+, 35S-compound 1 bound to several cell lines expressing both alpha4beta1 and alpha4beta7, but 2S-[(1-benzenesulfonyl-pyrrolidine-2S-carbonyl)-amino]-4-[4-methyl-2S-(methyl-[2-[4-(3-o-tolyl-ureido)-phenyl]-acetyl]-amino) pentanoylamino]-butyric acid (BIO7662), a specific alpha4beta1 antagonist, completely inhibited 35S-compound 1 binding, suggesting that alpha4beta1 was responsible for the observed binding. 35S-Compound 1 bound RPMI-8866 cells expressing predominantly alpha4beta7 with a KD of 1.9 nM in the presence of 1 mM Mn2+, and binding was inhibited only 29% by BIO7662, suggesting that the probe is a potent antagonist of activated alpha4beta7. With Ca2+/Mg2+, 35S-compound 1 bound Jurkat cells expressing primarily alpha4beta1 with a KD of 18 nM. In contrast, the binding of 35S-compound 1 to Mn2+-activated Jurkat cells occurred slowly, reaching equilibrium by 60 min, and failed to dissociate within another 60 min. The ability of four alpha4beta1/alpha4beta7 antagonists to block binding of activated alpha4beta1 or alpha4beta7 to vascular cell adhesion molecule-1 or mucosal addressin cell adhesion molecule-1, respectively, or to 35S-compound 1 was measured, and a similar rank order of potency was observed for native ligand and probe. Inhibition of 35S-compound 1 binding to alpha4beta1 in Ca2+/Mg2+ was used to identify nonselective antagonists among these four. These studies demonstrate that alpha4beta1 and alpha4beta7 have distinct binding properties for the same ligand, and binding parameters are dependent on the state of integrin activation in response to different divalent cations.

The alpha(4) integrin, alpha(4)beta(7), plays an important role in recruiting circulating lymphocytes to the gastrointestinal tract, where its ligand mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is preferentially expressed on high endothelial venules (HEVs). Dual antagonists of alpha(4)beta(1) and alpha(4)beta(7), N-(2,6-dichlorobenzoyl)-(L)-4-(2',6'-bis-methoxyphenyl)phenylalanine (TR14035) and N-(N-[(3,5-dichlorobenzene)sulfonyl]-2-(R)-methylpropyl)-(D)-phenylalanine (compound 1), were tested for their ability to block the binding of alpha(4)beta(7)-expressing cells to soluble ligand in suspension and under in vitro and in vivo shear flow. Compound 1 and TR14035 blocked the binding of human alpha(4)beta(7) to an (125)I-MAdCAM-Ig fusion protein with IC(50) values of 2.93 and 0.75 nM, respectively. Both compounds inhibited binding of soluble ligands to alpha(4)beta(1) or alpha(4)beta(7) on cells of human or rodent origin with similar potency. Under shear flow in vitro, TR14035 and compound 1 blocked binding of human alpha(4)beta(7)-expressing RPMI-8866 cells or murine mesenteric lymph node lymphocytes to MAdCAM-Ig with IC(50) values of 0.1 and 1 microM, respectively. Intravital microscopy was used to quantitate alpha(4)-dependent adhesion of fluorescent murine lymphocytes in Peyer's patch HEVs. When cells were prestimulated with 2 mM Mn(2+) to activate alpha(4)beta(7) binding to ligand, anti-alpha(4) monoclonal antibody (mAb) [10 mg/kg (mpk) i.v.] blocked adhesion by 95%, and anti-beta(1) mAb did not block adhesion, demonstrating that this interaction was dependent on alpha(4)beta(7). TR14035 blocked adhesion to HEVs [ED(50) of 0.01-0.1 mpk i.v.], and compound 1 blocked adhesion by 47% at 10 mpk i.v. Thus, alpha(4)beta(7)/alpha(4)beta(1) antagonists blocked alpha(4)beta(7)-dependent adhesion of lymphocytes to HEVs under both in vitro and in vivo shear flow.

Acylated beta-amino acids are described as potent, specific and orally bioavailable antagonists of VLA-4. The initial lead was identified from a combinatorial library. Subsequent optimization using a traditional medicinal chemistry approach led to significant improvement in potency (up to 8-fold) while maintaining good pharmacokinetic properties.