Modification of Peptides Using bis(thioether) ArylBridge (tABTM) Approach
- Technology Benefits
- Does not require use of expensive unusual amino acids and components; less expensive than staplingMay be performed on a solid support and in solution using unprotected peptidesMay be performed in water-based solventsMay be used to modify/stabilize alpha-helical and beta-hairpin peptidesAdditional versatility for modification and oligomerization of peptides
- Technology Application
- Production of peptide-based therapeutics
- Detailed Technology Description
- The novel approach developed from UCLA utilizes compounds for simultaneous S-alkylation of two strategically placed cysteine residues within the peptide, resulting in the formation of bis(thioether)-Aryl-Bridge (tABTM). The compounds necessary for this approach are both commercially available and inexpensive. The tABTM reaction can be performed both on resin and in solution. Two potential anticancer agents engineered by the tABTM approach possessed biological activity in vitro and in vivo.
- Supplementary Information
- Patent Number: WO2013173755A1
Application Number: WO2013US41650A
Inventor: RUCHALA, Piotr Pawel | MICEWICZ, Ewa, Dorota
Priority Date: 18 May 2012
Priority Number: WO2013173755A1
Application Date: 17 May 2013
Publication Date: 21 Nov 2013
IPC Current: C07K000100 | C07K000102 | C07K000764
Assignee Applicant: The Regents of the University of California
Title: MODIFICATION OF PEPTIDES USING A BIS(THIOETHER)ARYLBRIDGE APPROACH | MODIFICATION DE PEPTIDES PAR L'APPROCHE DU PONT BIS(THIOÉTHER)ARYLE
Usefulness: MODIFICATION OF PEPTIDES USING A BIS(THIOETHER)ARYLBRIDGE APPROACH | MODIFICATION DE PEPTIDES PAR L'APPROCHE DU PONT BIS(THIOÉTHER)ARYLE
Summary: The method is useful for stabilizing a peptide (claimed) which is useful: to treat cancer and viral infections; and to ameliorate at least one symptom of a pathology associated with an inflammatory response e.g. atherosclerosis. The anti-viral activity of the peptide against Urbani strain of severe acute respiratory syndrome Coronavirus, was tested in African green monkey kidney cells (Vero E6 cells) using in vivo assays. The results showed that the peptide DpV13 ST (Ile-Cys-Arg-Ile-Ile-Ile-Pro-Pro-Ile-Arg-Ile-Ile-Cys-CONH 2 ) exhibited an EC 50 value of 1.8 μ M.
Novelty: Stabilizing a peptide, useful e.g. to treat cancer, comprises providing a peptide containing at least two sulfur bearing residues and reacting peptide with di-halogeno-aryl-compound to form a bis(thioether)-aryl-bridge between the residues
- Industry
- Disease Diagnostic/Treatment
- Sub Category
- Cancer/Tumor
- Application No.
- 9556229
- Others
-
State Of Development
Some of the tAB-developed peptides showed in vitro and in vivo bioactivity.
Background
Stapled peptide technology utilizes chemical bonds to constrain peptides into α-helical conformations and results in an extension of potency due to increased resistance to proteases as well as greater cell permeability and bioactivity by the protein. Thus, stapled peptides have emerged as promising therapeutic candidates for treating a variety of human diseases. Numerous studies have been carried out to develop bioactive-stapled peptides. Among them, there are ring closing metathesis (RCM), azide-alkyne Huisgen cycloaddition (CuAAC), alkylation of cysteine, and lactam bridge formation. However, the RCM and CuAAC methods are very expensive and the latter two methods are generally low efficiency reactions. To address these problems, UCLA researchers have developed an alternative approach to producing stapled peptides that of very low cost and high efficiency.
Additional Technologies by these Inventors
- Anti-Obesity Compounds Derived from Neuromedin U
- Inhibitors Of Zika Virus
- Small-Molecule Inhibitors Of Zika Virus Infection
Tech ID/UC Case
23200/2012-754-0
Related Cases
2012-754-0
- *Abstract
-
Researchers in UCLA’s Department of Medicine have developed a novel peptide bridging technology that is a more efficient and cost-effective alternative to stapling technology for the manufacturing of peptide therapeutics.
- *IP Issue Date
- Jan 31, 2017
- *Principal Investigator
-
Name: Ewa Micewicz
Department:
Name: Piotr Ruchala
Department:
- Country/Region
- USA
