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Liberty Blue Customer Highlight: Dr. Fernando Ferrer

September 28, 2018

 

“The Liberty Blue is one of the best peptide synthesizers available in the market, facilitating the research in peptide chemistry and life sciences.”

Fernando J. Ferrer, Ph.D.

Senior Scientist, p53 Laboratory

Agency for Science, Technology & Research (A*STAR)

 

Dr. Fernando J. Ferrer has been working in peptide chemistry since 2001. Upon receiving his Ph.D. in 1999 from the University of Massachusetts under the supervision of Prof. L. A. Carpino, he accepted a position at The Burnham Institute in La Jolla, CA (now: Sanford Burnham Prebys Medical Discovery Institute). At The Burnham Institute, Dr. Ferrer ran a peptide facility in the Erkki Ruoslahti Laboratory for the synthesis of Arg-Gly-Asp (RGD) and tumor-homing peptides.

 

After five years at The Burnham Institute, Dr. Ferrer moved to Amylin Pharmaceuticals in San Diego, CA. In 2007, while working in Ved Srivastava’s group at Amylin, he first began using microwave technology (CEM Liberty) for solid-phase peptide synthesis. After observing great results with their first instrument, Amylin acquired a second unit and Dr. Ferrer was able to synthesize very important, but synthetically challenging, diabetes-related peptides, such as Human Nesfatin 1–82:

 

VPIDIDKTKVQNIHPVESAKIEPPDTGLYYDEYLKQVIDVLETDKHFREKLQKADIEEIKSGRLSKELDLVSHHVRTKLDEL

(Pseudoproline residues indicated by the dipeptides highlighted in blue.)

 

Then in 2013, after some positions with different CMOs, Dr. Ferrer joined the laboratory of Prof Sir David Lane, also known as the p53 Laboratory, at the Agency for Science, Technology, and Research (A*STAR) in Singapore. In the p53 Laboratory at A*STAR, Dr. Ferrer, in collaboration with Prof. Greg Verdine of Harvard University, works to develop and research the capabilities of stapled peptides in the p53 pathway. Their research is based on the MDM2–p53 interaction, and focuses on developing stapled peptides that are able to bind MDM2 and reactivate p53 functions. Importantly, p53 functions to prevent genome mutations and cancer/tumor formation.

 

Dr. Fernando Ferrer with two Liberty Blues in the p53 Laboratory
Figure 1. Dr. Fernando Ferrer with two Liberty Blues in the p53 Laboratory.

 

In 2015, the p53 Laboratory acquired their first CEM Liberty Blue automated microwave peptide synthesizer, and in 2018 the group acquired their second unit (Figure 1). Dr. Ferrer and the p53 Laboratory have successfully utilized their Liberty Blues for the microwave-assisted synthesis of their benchmark peptides, including the synthesis of stapled peptide VIP116 (Figure 2).

 

i, i+7 Ring closing metathesis for VIP116 peptide.

Figure 2. i, i+7 Ring closing metathesis for VIP116 peptide.

 

The Liberty Blue has proved an effective instrument for the group. In a double blind study comparing the biological activity of VIP116 synthesized with conventional methods versus with the Liberty Blue, no difference was found (Figure 3).

 

Double blind test. P53 activation assay – Comparing different methods of synthesis on T22 Cells

Figure 3. Double blind test. P53 activation assay – Comparing different methods of synthesis on T22 Cells.

 

In addition to the microwave-assisted synthesis of stapled peptides, the p53 Laboratory is also harnessing the power of microwaves with their new Pepcohol resins (patent pending) for the synthesis of peptide alcohols and peptaibols. Notably, Dr. Ferrer and the p53 Laboratory have been able to synthesize Octreotide (peptide alcohol) and Alameticin F30 (peptaibol) in good yield and purity:

 

D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-ol (Octreotide) and Ac-Aib-Pro-Aib-Ala-Aib-Ala-Gln-Aib-Val-Aib-Gly-Leu-Aib-Pro-Val-Aib-Aib-Glu-Gln-Phe-ol (Alameticin)

(Alcohol C-terminus indicated by the residues highlighted in blue.)

 

In summary, Dr. Ferrer and the p53 Laboratory have capitalized on the versatility and efficiency of the Liberty Blue automated microwave peptide synthesizer, both by synthesizing more than 20 different stapled peptides (in over 100 total successful syntheses) and in developing their new Pepcohol resins. Dr. Fernando Ferrer concluded, “The Liberty Blue is one of the best peptide synthesizers available in the market, facilitating the research in peptide chemistry and life sciences.”

 

 

For A Selection of Relevant Publications from the p53 Laboratory, see:

“Structure-activity studies of Mdm2/Mdm4-binding stapled peptides compromising non-natural amino acids” PLOS ONE, 2017, 12, 1–15. DOI: 10.1371/journal.pone.0189379

“Assessing the Efficacy of Mdm2/Mdm4-Inhibiting Stapled Peptides Using Cellular Thermal Shift Assays” Scientific Reports, 2015, 5, 1–9. DOI: 10.1038/srep12116

“Stapled Peptides with Improved Potency and Specificity That Activate p53” ACS Chemical Biology, 2013, 8, 506–512. DOI: 10.1021/cb3005148