This Review explores the class of plant-derived macrocyclic peptides called cyclotides. We
include an account of their discovery, characterization, and distribution in the plant kingdom …

Bioactive peptides have potential as drug leads, but turning them into drugs is a challenge
because of their typically poor metabolic stability. Molecular grafting is one approach to …

Mast cells are rich in proteases, which are the major proteins of intracellular granules and
are released with histamine and heparin by activated cells. Most of these proteases are …

Cell-penetrating peptides can translocate across the plasma membrane of living cells and
thus are potentially useful agents in drug delivery applications. Disulfide-rich cyclic peptides …

Cyclotides are plant-derived peptides with complex structures shaped by their head-to-tail
cyclic backbone and cystine knot core. These structural features underpin the native …

Cyclotides are plant-derived cyclic peptides that have a head-to-tail cyclic backbone and
three conserved disulphide bonds that form a cyclic cystine knot motif. They occur in plants …

Highlights•Cyclotides are ultra-stable and tolerant to sequence substitutions in all
loops.•Sequences grafted into a cyclotide scaffold are stabilized and generally maintain …

Non-immunoglobulin based protein scaffolds have been reported as promising alternatives
to traditional monoclonal antibodies for over a decade and are often mentioned as part of …

Highlights•Knottins are small constrained peptides with ultra-high stability.•New binding
epitopes can be introduced into natural knottins using protein engineering.•Knottins have …

Cyclotides are a large family of plant peptides that are structurally defined by their cyclic
backbone and a trifecta of disulfide bonds, collectively known as the cyclic cystine knot …