From Review Papers

 

http://www.nature.com/nature/journal/v537/n7620/pdf/nature19949.pdf

(Mass-Spectrometric exploration of proteome structure and function)

-> Provide unprecedented insights into the composition, structure, function and control of the proteome, shedding light on complex biological processes and phenotypes.

- Mass-Spectrometry-based methods

-> Capability to identify conclusively and quantify accurately almost any protein that has been expressed.

-> Systematically identify and localize modified amino acids in the polypeptide chain as well as determine the composition, stoichiometry and topology of the subunits of multiprotein complexes and even contribute to determining their structure.

-> Make possible the systematic analysis of the proteome to an extent that had been predicted previously

 

https://www.ncbi.nlm.nih.gov/pubmed/12634792

(From genomics to proteomics.)

- Proteomics would not be possible without the previous achievements of genomics, which provided the ‘blueprint’

of possible gene products that are the focal point of proteomics studies.

- The ability of mass spectrometry to identify ever smaller amounts of protein from increasingly complex mixtures is a

primary driving force in proteomics, as described in the review on page 198 by Aebersold and Mann.

Proteomics is set to have a profound impact on clinical diagnosis and drug discovery, as is fittingly reviewed by Sam Hanash on page 226, the inaugural president of HUPO.

Because most drug targets are proteins, it is inescapable that proteomics will enable drug discovery, development and clinical practice.

 

https://www.ncbi.nlm.nih.gov/pubmed/?term=metabolomics%3A+the+apogee+of

(Innovation: Metabolomics: the apogee of the omics trilogy.)

 - metabolites serve as direct signatures of biochemical activity and are therefore easier to correlate with phenotype.

 - metabolites serve as direct signatures of biochemical activity

 - The untargeted [metabolomic] workflow is global in scope and outputs data related to comprehensive cellular metabolism.

- In particular, it has been useful in identifying altered metabolic pathways in disease that represent novel drug targets: an evolving biomedical application referred to as ‘therapeutic metabolomics’

- Another area is in characterizing gene and protein function. In addition to successfully identifying the function of unknown genes and proteins, untargeted profiling has been applied to discover new functions for known genes and proteins.

 

https://www.ncbi.nlm.nih.gov/pubmed/27140638

(Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles.)

*Rosi ->PPAR activity increase

(1)Expression of uncoupling protein(UCP1) increase

-> Transformation (WAT->Brown-like adipose tissue) & Angiogenesis increase

(2) Expression of VEGF& Angiopoietin-like 4 increase

-> Adipose tissue angiogenesis increase

*PGE2(Prostaglandin E2)

-> Activate Prostaglandin receptor  -> UCP1 Expression increase ->Adipose tissue transformation increase

*Increased Angiogenesis

=> Mobility of Targeted NPs to Adipose angiogenic vessel increase(Efficiency increase)

 

(http://www.nature.com/nm/journal/v22/n7/full/nm0716-694.html)

All in one: Researchers create combination drugs for diabetes and obesity

 

Novelty of the combinations

-> Use protein engineering and chemistry

-> Combine two or more agents into a single molecule.

 

(1) GLP-1 Glucagon dual agonist

-> combine GLP-1(glucagon-like peptide 1) with Glucagon

-> Showed a nearly 5-pound weight loss in a dozen individuals

-> Suppress food intake

* Glucagon

-> Releases glucose into the bloodstream (unwise choice for an antidiabetic agent.)

-> Buffer the side effects of GLP-1 (when given in tandem)

-> the combination is more effective at lowering body weight than either of its components alone.

 

 

 

 

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Scientific Background