The influence of peptide impurity profiles on functional tissue-organ bath response: the 11-mer peptide INSL6[151-161] case.
Bioactive peptides have great pharmaceutical potential as nutraceuticals, diagnostics, and therapeutic drugs in several clinical areas. Thus, the search for novel lead peptides with a biological function has attracted renewed interest. Crude peptide material (i.e., ~70% purity) of INSL6[151-161] (NH₂-FRSLFWGNHSQ-COOH) was found to trigger a contractile response in guinea pig ileum longitudinal smooth muscle preparations using tissue-organ baths. However, the purified peptide (i.e., ≥ 95% purity) had no effect on this model. Further investigation with crude materials from other suppliers, with purities ranging between 50% and 80%, indicated that the crude products gave a false-positive functional tissue-organ bath conclusion. These observations question the functionality conclusions when using crude-purity peptide materials; during the initial research or discovery phase, peptide quality is generally neglected, possibly leading to misinterpretation of biological results due to by-products from peptide synthesis and, thus, wrong fail/pass decisions. Therefore, we strongly recommend appropriate quality control testing before using any peptides for initial biomedical research or discovery purposes.
Drug Quality and Registration (DruQuaR) Group, Faculty of Pharmaceutical Sciences, Ghent University, B-9000 Ghent, Belgium.
Mathieu
M
Verbeken
Evelien
E
Wynendaele
Romain A
RA
Lefebvre
Els
E
Goossens
Bart De
BD
Spiegeleer
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000494:pharmacology*; D013058:Mass Spectrometry / Q000379:methods; D009130:Muscle, Smooth / Q000187:drug effects; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D011786:Quality Control; D013056:Spectrophotometry, Ultraviolet
C512663:INSL6 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides