Peptides International can produce 36 peptides in afour-to-five day period, depending on length and sequence, running itsautomated small-scale synthesizer around the clock.
"This makes us competitive with Asian outfits," says PIPresident and Chief Operating Officer Dr. Michael Pennington.
In addition, Pennington notes, the company has custompeptide synthesis expertise across a wide range of technologies, frommulti-disulfide peptides to multistep organic synthesis. PI also offers anextensive portfolio of building blocks and other peptide synthesis tools, andits activities have recently been certified to ISO 9001:2008 standards.
With 25 years of experience in peptide manufacturing,Peptisyntha, a wholly owned company of Solvay, provides a seamless portfolio ofexpertise from lead optimization to commercial cGMP manufacturing. Peptisynthahas developed and demonstrated expertise in the design of cost-effectivepeptide manufacturing processes and in the cGMP production of clinical andcommercial peptide APIs. Its facilities have had numerous successful U.S. Foodand Drug Administration and European Medicines Agency inspections and offer afull range of solid-phase (SPPS), liquid-phase (LPPS) and hybrid synthesiscapabilities. With GMP manufacturing facilities in the United States andBelgium, Peptisyntha supports all manufacturing technologies (SPPS, LPPS andhybrid approaches) at all scales.
One reason for heightened interest in peptide chemistry isthe challenge posed by the problem of drug delivery through the cell membranein order to treat and manage diseases and conditions as diverse as HIV andconstipation. The discovery of cell-penetrating peptides (CPPs) represented amajor breakthrough for the transport of large-cargo molecules that may beuseful in clinical applications. CPPs are able to translocate over membranesand gain access to the cell interior, delivering large-cargo molecules, such asoligonucleotides, into cells.
Pennington cites a number of sulfide-bearing peptides, manyof which are derived from venom. Fuzeon (Enfuvirtide injection) is a 39-residuepeptide used in combination with other drugs to treat HIV infection in peoplewho have not responded well enough to other antiviral medications. Enfuvirtideis in a class of medications called HIV fusion inhibitors. It works by stoppingHIV from infecting healthy cells.
Because chemotherapy has unwanted side effects and killshealthy tissue around the tumor, researchers have long been interested indeveloping alternative forms of therapy. The aim of targeted therapies, as thename implies, is to target cancerous cells while leaving surrounding cellsunaffected.
One type of targeted therapy that looks promising against glioblastomais based on the venom of the yellow Israeli scorpion, Leiurus quinquestriatus.The venom is among the most toxic of all scorpion venoms; it containshistamine, enzymes, enzyme inhibitors and the potent neurotoxins chlorotoxinand charbydotoxin, which specifically target low-conductance glioma-chloridechloride channels (GCC) and high-conductance calcium-gated potassium channels,respectively.
Byetta is derived from gila monster venom, Pennington notes,and is approved to treat type 2 diabetes, both by itself and in combinationwith certain oral diabetes medications. Byetta comes in an injection form andworks by increasing insulin production after meals and decreasing the amount ofsugar produced by the liver. As a result, Byetta can help lower blood sugarlevels, which can decrease the risks of developing long-term problemsassociated with diabetes, including heart disease.
Finally, Linaclotide is a 15-residue peptide with threedisulfide units that can be given orally to relieve constipation, while SHK isa potassium channel blocker derived from sea anemone toxin that is enteringclinical trials for multiple sclerosis and is a candidate for preventingtransplant rejection and in the treatment of other autoimmune diseases.