Compounds and methods for modulating cell adhesion

Inactive Publication Date: 2006-08-17
ADHEREX TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0056] In another embodiment, there are provided methods for facilitating the removal of hair follicles from skin, e.g., viable or intact hair follicles, comprising contacting a cadherin expressing cell with, or administering to a mammal, a cell adhes

Problems solved by technology

The formation of such junctions gives rise to physical and permeability barriers that restrict the free passage of cells and other biological substances from one tissue compartment to another.
Although cell adhesion is required for certain normal physiological functions, there are situations in which cell adhesion is undesirable.
Cancer is a significant health problem throughout the world.
Although advances have been made in detection and therapy of cancer, no universally successful method for the prevention or treatment of human cancer is currently available.
Treatment is commonly based on surgery and/or radiation therapy, but these methods are ineffective in a significant percentage of cases, and this prevalent disease is currently the second leading cause of cancer death among men in the U.S.
Such inhibition may be the result of pathology or injury involving severed neuronal connections and/or spinal cord damage.
However, previous attempts to promote neurite outgrowth have achieved limited success due, in part, to difficulties associated with maintaining continuous growth over a particular defined region.
In addition, permeability barriers arising from cell adhesion create difficulties for the delivery of drugs to specific tissues and tumors within the body.
However, the use of skin patches has been limited to small, hydrophobic molecules

Method used

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  • Compounds and methods for modulating cell adhesion
  • Compounds and methods for modulating cell adhesion
  • Compounds and methods for modulating cell adhesion

Examples

Experimental program
Comparison scheme
Effect test

Example

Example 1

Preparation of Representative Cyclic Peptides

[0380] This Example illustrates the solid phase synthesis of representative cyclic peptides.

[0381] Peptides were generally assembled on methylbenzhydrylamine resin (MBHA resin) for the C-terminal amide peptides. The traditional Merrifield resins were used for any C-terminal acid peptides. Bags of a polypropylene mesh material were filled with the resin and soaked in dichloromethane. The resin packets were washed three times with 5% diisopropylethylamine in dichloromethane and then washed with dichloromethane. The packets are then sorted and placed into a Nalgene bottle containing a solution of the amino acid of interest in dichloromethane. An equal amount of diisopropylcarbodiimide (DIC) in dichloromethane was added to activate the coupling reaction. The bottle was shaken for one hour to ensure completion of the reaction. The reaction mixture was discarded and the packets washed with DMF. The N-α-Boc was removed by acidolysis ...

Example

Example 2

Disruption of the Ability of Mouse Cerebellar Neurons to Extend Neurites

[0384] Three cell adhesion molecules, N-cadherin, N-CAM and L1, are capable of regulating neurite outgrowth (Doherty and Walsh, Curr. Op Neurobiol. 4:49-55, 1994; Williams et al., Neuron 13:583-594, 1994; Hall et al., Cell Adhesion and Commun. 3:441-450, 1996; Doherty and Walsh, Mol. Cell. Neurosci. 8:99-111, 1994; Safell et al., Neuron 18:231-242, 1997). Neurons cultured on monolayers of 3T3 cells that have been transfected with cDNAs encoding N-cadherin, N-CAM or L1 extend longer neurites than neurons cultured on 3T3 cells not expressing these cell adhesion molecules. This Example illustrates the use of a representative cyclic peptide to inhibit neurite outgrowth.

[0385] Neurons were cultured on monolayers of 3T3 cells transfected with cDNA encoding N-cadherin essentially as described by Doherty and Walsh, Curr. Op. Neurobiol. 4:49-55, 1994; Williams et al., Neuron 13:583-594, 1994; Hall et al., Cel...

Example

Example 3

Disruption of Bovine Endothelial Cell Adhesion

[0388] This Example illustrates the use of representative cyclic peptides to disrupt adhesion of endothelial cells, which express N-cadherin.

[0389] Bovine pulmonary artery endothelial cells were harvested by sterile ablation and digestion in 0.1% collagenase (type II; Worthington Enzymes, Freehold, N.J.). Cells were maintained in Dulbecco's minimum essential medium (Clonetics, San Diego, Calif.) supplemented with 10% fetal calf serum (Atlantic Biologicals, Nor cross, GA) and 1% antibiotic-antimycotic at 37° C. in 7% CO2 in air. Cultures were passaged weekly in trypsin-EDTA (Gibco, Grand Island, N.Y.) and seeded onto tissue culture plastic at 20,000 cell / cm2 for all experiments. Endothelial cultures were used at 1 week in culture, which is approximately 3 days after culture confluency was established. The cells used in all protocols were between 4th passage and 10th passage. The cells were seeded onto coverslips and treated 30...

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Abstract

Cyclic peptides comprising a cadherin cell adhesion recognition sequence HAV, and compositions comprising such cyclic peptides, are provided. Methods for using such peptides for modulating cadherin-mediated cell adhesion in a variety of contexts are also provided.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation-in-part of U.S. application Ser. No. 10 / 464,071, filed Jun. 18, 2003, now pending; which application is a continuation of U.S. application Ser. No. 09 / 544,782, filed Apr. 7, 2000, now pending; which application is a continuation-in-part of U.S. application Ser. No. 09 / 458,870, filed Dec. 10, 1999, now issued as U.S. Pat. No. 6,465,427; which application is a continuation-in-part of U.S. application Ser. No. 09 / 357,717, filed Jul. 20, 1999, now issued as U.S. Pat. No. 6,417,325; which application is a continuation-in-part of U.S. application Ser. No. 09 / 248,074, filed Feb. 10, 1999, now issued as U.S. Pat. No. 6,346,512; which application is a continuation-in-part of U.S. application Ser. No. 08 / 996,679, filed Dec. 23, 1997, now issued as U.S. Pat. No. 6,169,071; which application is a continuation-in-part of U.S. application Ser. No. 08 / 893,534, filed Jul. 11, 1997, which application is now issued as U...

Claims

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Application Information

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IPC IPC(8): A61K38/12C07K7/64A61K39/395C07K16/30A61K38/00A61K38/17C07K7/06C07K7/56C07K14/705
CPCA61K38/00C07K7/06C07K7/56C07K7/64C07K14/705
Inventor BLASCHUK, ORESTGOUR, BARBARAFAROOKHI, RIAZALI, ANMARGEORGE, SARAH
Owner ADHEREX TECH
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