Title:
STRUCTURAL DESIGN OF FLEXIBLE DISKS TO MODULATE MECHANOTRANSDUCTION MEDIATED BY INTEGRIN RECEPTORS
Document Type and Number:
WIPO Patent Application WO/2023/195577
Kind Code:
A1
Abstract:
Substances in the form of flexible disks to modulate mechanotransduction mediated by integrins were designed. Two main ideas for the design are as follows. First, the radius of the disk can be prescribed to specify the radius of mechanically perturbed integrin clusters. By using disks with a greater radius value, the vinculin binding site activation vs. force relation can be amplified and shifted to the positive direction along the input axis. Second, by recruiting a certain integrin whose affinity values to talins are higher than those of other integrins into the cluster, the radial distance from the center of clusters to the point where the membrane tightly adheres to the cytoskeleton can be decreased. This results in the increase of the maximum slope of the vinculin binding site activation vs. force relation. The design can be used in the development of drugs for diseases associated with dysfunctions in integrin-mediated systems.
Inventors:
KIM JICHUL (KR)
Application Number:
PCT/KR2022/007963
Publication Date:
October 12, 2023
Filing Date:
June 06, 2022
Export Citation:
Assignee:
KIM JICHUL (KR)
International Classes:
A61K9/51; A61K38/00; C07K5/09; C07K5/113; C07K7/06; C07K7/08
Foreign References:
| US20140353172A1 | 2014-12-04 | |||
| KR20220048697A | 2022-04-20 | |||
| US20050058842A1 | 2005-03-17 |
Other References:
HERNANDEZ-GORDILLO, VICTOR ET AL.: "Fully synthetic matrices for in vitro culture of primary human intestinal enteroids and endometrial organoids", BIOMATERIALS, vol. 254, no. 120125, 2020, pages 1 - 49, XP086169293, DOI: 10.1016/j.biomaterials.2020.120125
SCHWARTZ M. A.: "Integrins and Extracellular Matrix in Mechanotransduction", COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, vol. 2, no. 12, 1 December 2010 (2010-12-01), pages a005066 - a005066, XP093097859, DOI: 10.1101/cshperspect.a005066
ZHAO JUNWEI, SANTINO FEDERICA, GIACOMINI DARIA, GENTILUCCI LUCA: "Integrin-Targeting Peptides for the Design of Functional Cell-Responsive Biomaterials", BIOMEDICINES, vol. 8, no. 9, pages 307, XP093097861, DOI: 10.3390/biomedicines8090307
SCHWARTZ M. A.: "Integrins and Extracellular Matrix in Mechanotransduction", COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, vol. 2, no. 12, 1 December 2010 (2010-12-01), pages a005066 - a005066, XP093097859, DOI: 10.1101/cshperspect.a005066
ZHAO JUNWEI, SANTINO FEDERICA, GIACOMINI DARIA, GENTILUCCI LUCA: "Integrin-Targeting Peptides for the Design of Functional Cell-Responsive Biomaterials", BIOMEDICINES, vol. 8, no. 9, pages 307, XP093097861, DOI: 10.3390/biomedicines8090307
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