Inhibitor of cell adhesion

M. Aumailley, M. Gurrath, G. Muller, J. Calvete, R. TimpI, H. Kessler, Arg-Gly-Asp constrained within cyclic pentapeptides, strong and selective inhibitors of cell adhesion to vitronectin and laminin fragment PI, FEBS. Lett. 291(1) (1991) 50-54. 

The trisaccharide itself should be a competitive inhibitor of cell adhesion if the trisaccharide unit of the glycoprotein is critical for the interaction. 

Antagonists of Integrin Binding as Inhibitors of Cell Adhesion. 412... 

M. Rosch, H. Herzner, W. Dippold, M. Wild, D. Vestweber, and H. Kunz, Synthetic inhibitors of cell adhesion A glycopeptide from E-selectin ligand 1 (ESL-1) with the arabino sialyl Lewis structure, Angew. Chem. Int. Ed., 40 (2001) 3836-3839. 

In the search for inhibitors of cell adhesion molecule expression in human endothelial cells, thieno[23-d]pyrimidin-4-one 36 was first subjected to a Krapcho dccarboethoxylation. The resultant pyrimidone was then converted to 4-chlorothieno[23-leaving group, new C-S and C-N bond formations were easily achieved by SnAf displacements to produce 38 <01JMC988>. Yields were not given for all compounds... 

Amemiya, M., T. Someno, R. Sawa, H. Naganawa, M. Ishizuka, and T. Takeuchi Cytostatin, a Novel Inhibitor of Cell Adhesion to Components of Extracellular Matrix Produced by Streptomyces sp. MJ654-NF4. J. Antibiot., 47, 541 (1994). 

Subsequently, through culture of the same fungus, Periconia byssoides, collected from the same mollusk, Aplysia kurodai, the same team isolated a series of irregular sesquiterpenes, peribysins A-D, which are inhibitors of cell adhesion of HL-60 (human leukemia) on HUVECs (human umbilical vein endothelial cells) and could be useful for the treatment of metastasis. Peribysin D is 380 times more active than herbimycin A, which is used as a standard (Yamada et al., 2004). 

Rao, N., Meldal, M., Bock, K., and Hindsgaul, O. Library of glyco-peptides useful for identification of cell adhesion inhibitors, Glycomed Corp., 664, 303 [5,795,958], U.S. Patent 1-28, Califomia/USA. 

As stated earlier, activation of endothelial cells by pro-inflammatory stimuli leads to the expression of cell adhesion molecules and cytokines such as IL-6 and IL-8. The expression and hence modulation of surface expressed adhesion molecules by e.g. targeted delivery of inhibitors of NFkB, can be measured using flow cytometric analysis or whole cell ELISA techniques. Cytokine production can be measured in the supernatant of cultured cells or in biological fluids. Furthermore, competitive or quantitative RT-PCR analysis of mRNA levels of cell adhesion molecules or cytokines, allows the transcriptional activity of the genes of interest to be estimated. 

The quaternization method is also highlighted by the short asymmetric synthesis of cell adhesion molecule BIRT-377 (Scheme 5.24), which is a potent inhibitor of the interaction between intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) [16]. Thus, asymmetricp-bromobenzylation of the alanine derivative 42 (R1 = Me) with (S)-18 under similar phase-transfer conditions as described above gave rise to p-bromobenzylalanine ester 10 in 97% ee (83% yield). A similar asymmetric p-bromobenzylation of alanine ethyl ester 42 (R1 = Me, R= Et) gave the amino ester 47 (R= Et) in 90% ee (86% yield). The amino ester 47 (R = t-Bu or Et) was treated with 3,5-dichlorophenyl isocyanate in the presence of sodium carbonate in dimethylsulfoxide (DMSO) to furnish the hydantoin 48 in 86%... 

Hayashi, M., Kim, Y.-R, Hiraoka, H., Natori, M., Takamatsu, S., Kawakubo, T, Masuma, R., Komiyama, K., and Omura, S. (1995). Macrosphelide, a novel inhibitor of cell-cell adhesion molecule. I. Taxonomy, fermentation, isolation and biological activities. J. Antibiot. 48, 1435-1439. 

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