Antiangiogenic activity of 2-formyl-8-hydroxy-quinolinium chloride.

Tumour growth is closely related to the development of new blood vessels to supply oxygen and nutrients to cancer cells. Without the neovascular formation, tumour volumes cannot increase and undergo metastasis. Antiangiogenesis is one of the most promising approaches for antitumour therapy. The exploration of new antiangiogenic agents would be helpful in antitumour therapy. Quinoline is an aromatic nitrogen compound characterized by a double-ring structure which exhibits a benzene ring fused to pyridine at two adjacent carbon atoms. The high stability of quinoline makes it preferable in a variety of therapeutic and pharmaceutical applications, including antitumour treatment. This work is to examine the potential antiangiogenic activity of the synthetic compound 2-Formyl-8-hydroxy-quinolinium chloride. We found that 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of human umbilical vein endothelial cells in vitro. Using the diethylnitrosamine-induced hepatocarcinogenesis model, 2-Formyl-8-hydroxy-quinolinium chloride showed strong antiangiogenic activity. Furthermore, 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of large Hep3B xenografted tumour from the nude mice. We assume that 2-Formyl-8-hydroxy-quinolinium chloride could be a potential antiangiogenic and antitumour agent and it is worthwhile to further study its underlying working mechanism.

5-(Dimethylamino)-N-(4-ethynylphenyl)-1-naphthalenesulfonamide as a novel bifunctional antitumor agent and two-photon induced bio-imaging probe.

A novel compound, (5-(dimethylamino)-N-(4-ethynylphenyl)-1-naphthalenesulfonamide), was prepared and characterized; it shows dual functional roles as an effective antitumor and a two-photon induced bio-imaging agent.

Amino acid sequence of rabbit skeletal muscle myosin. 50-kDa fragment of the heavy chain.

The amino acid sequence of the 50-kDa fragment that is released by limited tryptic digestion of the head portion of rabbit skeletal muscle myosin was determined by analysis and alignment of sets of peptides generated by digestion of the fragment at arginine or methionine residues. This fragment contains residues 205-636 of the myosin heavy chain; among the residues of particular interest in this fragment are N epsilon-trimethyllysine, one of four methyl-amino acids in myosin, and Ser-324, which is photoaffinity labeled by an ATP analogue (Mahmood, R., Elzinga, M., and Yount, R. G. (1989) Biochemistry 28, 3989-3995). Combination of this sequence with those of the 23- and 20-kDa fragments yields an 809-residue sequence that constitutes most of the heavy chain of chymotryptic S-1 of this myosin.

The sequence of the NH2-terminal 204-residue fragment of the heavy chain of rabbit skeletal muscle myosin.

The amino acid sequence of the Mr = 23,000 peptide that is generated by limited tryptic digestion of rabbit skeletal muscle heavy meromyosin was determined. This fragment represents the NH2-terminal 204 residues of the heavy chain of myosin, and its sequence is (formula; see text) This peptide contains the lysine residue (Lys 83) whose reaction with 2,4,6,-trinitrobenzenesulfonate alters the enzymatic activity of myosin, as well as two types of methylated lysines. Position 34 is occupied by epsilon-N-monomethyllysine and lysine in an approximate 60:40 ratio, while position 129 is fully occupied by one of the two epsilon-N-trimethyllysines in myosin heavy chain. There is evidence suggesting that this fragment contains residues that contribute to the ATP-binding site of myosin; the sequence surrounding the epsilon-N-trimethyllysine is devoid of charges and could form a hydrophobic pocket for binding of the adenine moiety while the epsilon-N-trimethyllysine, which carries a positive charge at all pH values, could bind an ATP phosphate group.

Cloned mRNA sequences for two types of embryonic myosin heavy chains from chick skeletal muscle. I. DNA and derived amino acid sequence of light meromyosin.

Two myosin heavy chain cDNA clones (251 and 110), constructed from chick embryonic skeletal muscle mRNA, were subjected to extensive DNA sequence analysis. A complete description of the DNA sequence of clone 251 was obtained. This 1.5-kilobase pair cDNA sequence specified the COOH-terminal 439 amino acids of the myosin heavy chain, and included the entire 3' nontranslated region. The translated and 3' nontranslated sequences were purine- (64%) and AT-(71%) rich, respectively. The derived amino acid sequence of clone 251 correlated well with sequences obtained by direct amino acid sequencing of adult rabbit back muscle myosin heavy chain protein (87% homology), as well as with cloned myosin heavy chain sequences from other species. Comparison of clone 251 with a partial DNA sequence of clone 110 revealed significant structural differences both in the translated, and 3' nontranslated regions. This data indicates that these two clones represent two distinct myosin heavy chain genes. The protein sequence specified by clone 251 corresponds to the light meromyosin portion of the myosin heavy chain rod. These sequences, like other myosin heavy chain rod sequences, are alpha-helical and exhibit 7- and 28-residue periodicities in the linear distribution of nonpolar, and basic and acidic amino acids, respectively.