Three macrocyclic trypsin inhibitors from Momordica cochinchinensis seeds are the smallest known naturally occurring circular peptides, with a unique atypical backbone cyclization mechanism.
Smallest natural cyclesMCoTI peptides at ~34 amino acids are the smallest known naturally occurring cyclic peptides, more drug-like than larger cyclotides
What the researchers found
Three macrocyclic trypsin inhibitors (MCoTI-I, -II, -III) from Momordica cochinchinensis are the smallest known naturally cyclic peptides, with atypical backbone cyclization and potent trypsin inhibition.
Why it matters
Smaller cyclic peptides are easier to synthesize and more drug-like. These squash-derived miniature cyclotides expand the available toolkit for designing stable circular peptide drugs.
How the study worked
In-vitro study using gel filtration, ion exchange, and reverse-phase HPLC to isolate and sequence three cyclic peptides from squash seeds. Structure determined by proteolytic cleavage analysis.
What this study cannot tell us
Structural characterization without biological activity beyond trypsin inhibition. The therapeutic potential needs to be explored through grafting experiments.
How to read the evidence
Moderate evidence from peptide isolation and structural characterization with clear novelty in size and cyclization mechanism.
When this study was published
Published in 2000. MCoTI peptides have since become one of the most-used cyclotide scaffolds in drug design, with grafted variants targeting cancer and other diseases.
The bigger picture
Nature provides diverse circular peptide scaffolds of varying sizes. The MCoTI family offers a smaller, potentially more drug-like option than the larger cyclotides for engineering stable peptide therapeutics.
Questions still open
- Can bioactive sequences be grafted into the MCoTI scaffold?
- What advantage does the smaller size offer for drug delivery?
- Does the atypical cyclization mechanism affect stability?
Common questions
Why are circular peptides from plants useful for drugs?
What are they used for now?
Read the original research
Squash trypsin inhibitors from Momordica cochinchinensis exhibit an atypical macrocyclic structure.
Biochemistry, 39(19), 5722-30
Citation
Hernandez, J F; Gagnon, J; Chiche, L; Nguyen, T M; Andrieu, J P; Heitz, A; Trinh Hong, T; Pham, T T; Le Nguyen, D. (2000). Squash trypsin inhibitors from Momordica cochinchinensis exhibit an atypical macrocyclic structure.. Biochemistry, 39(19), 5722-30.