Why is protein cyclisation desirable?

Question

There are a number of methods to "cyclize" an existing peptide:

• Disulphide bond as described in Disulfide Bond Mimetics: Strategies and Challenges by Gori et al.
• "Linchpin" based (linker chemistry) as described in Synthetic Cross-linking of Peptides: Molecular Linchpins for Peptide Cyclization by Derda et al.

Why would the "cyclization" of a protein be a desirable goal?

Answer 1

As described in the abstract of Synthetic Cross-linking of Peptides: Molecular Linchpins for Peptide Cyclization by Derda et al., protein cyclization improves:

resistance to proteolytic degradation and conformational stability. The latter property leads to an increase in binding potency and increased bioavailability due to increased permeation through biological membranes.

In simpler terms, a protein that is cyclized is less likely to:

1. Fold into an unhelpful shape.
2. Be broken up by an enzyme.

Thus, they are more likely to:

1. Act as better binders for a given target
2. Make it across a cell membrane