Natural vs. Combichem Approach
Systematic screening of peptides is a well-established approach. The peptides can be naturally derived or chemically synthesized, with the latter method being more prevalent.
Ambryx Biotechnology (www.ambryxbiotech.com) performs systematic screening of naturally derived peptides. It has an anticancer peptide in the preclinical stage with three more in R&D. “We assessed secreted protein fractions derived from embryonic cells for apoptotic effects in multiple in vitro cancer cell models. We discovered a native protein that binds to zinc resulting in a conformation change revealing active peptide domains that have anticancer activity. We subsequently isolated the active peptide domain,“ says Helen Chen, Ph.D., vp of business development at Ambryx.
Ambryx´ anticancer peptide drug has natural glycosylation, so it has the potential to last longer in vivo and be truly bioavailable. “The peptide was 8 to 10 times more active than native protein as it does not require zinc for activity,“ says Dr. Chen. The company is currently gathering data in animal obesity models.
Advances in understanding how to modulate peptides have resulted in novel peptides for screening, according to Christopher Holmes, Ph.D., senior director of chemistry at Affymax (www.affymax.com). Affymax leverages its combichem expertise for peptide drug discovery.
The company´s four-step process starts by identifying peptides of interest, synthesizing peptide analogs, analyzing both sequence and architecture, and studying effects in animal models of disease. “We use PEGitecture, which is the simultaneous study of architecture and PEGylation, to modulate activity and increase peptide half-life,“ explains Dr. Holmes.
“Our main focus in peptide therapeutics is in nephrology and oncology,“ says Mary Fermi, senior director of commercial development at Affymax. “We are developing Hematide, a synthetic peptide-based erythropoiesis-stimulating agent that stimulates red blood cell production.“
Potential benefits of Hematide include good tolerance, low immunogenicity, simple and less frequent dosing, and sustained increase in red blood cell production, the company says. It is in Phase II trials for the treatment of anemia in chronic kidney disease and cancer and in Phase II dose-finding trial for treatment of anemia in cancer chemotherapy patients.