What is the Origin of Cyclization of Peptides?

This concept originates from organic chemistry and medicinal chemistry, particularly in the design and optimization of peptide-based therapeutics. Naturally occurring cyclic peptides, such as somatostatin, demonstrated the physiological advantages of this structure in terms of stability and function. Synthetic cyclization techniques were developed to mimic these natural advantages and overcome the inherent pharmacokinetic limitations of linear peptides in clinical use.

What is the Mechanism of Cyclization of Peptides?

The mechanism involves the formation of a covalent bond between the N-terminus and C-terminus, or between reactive side chains of amino acids within the sequence, such as disulfide bonds between cysteine residues. By locking the peptide into a specific, biologically active conformation, cyclization reduces the entropic penalty associated with receptor binding. This constrained structure improves receptor engagement, translating into enhanced hormonal signaling efficacy and a more predictable clinical effect.

Cyclization of Peptides ∞ Area

Cyclization of Peptides

Meaning

Cyclization of peptides is a post-translational or synthetic chemical modification process where a linear chain of amino acids is covalently linked to form a circular structure. This structural change significantly enhances the peptide’s resistance to enzymatic degradation by proteases, dramatically increasing its in vivo half-life and bioavailability. The cyclic conformation also restricts the peptide’s flexibility, often leading to a higher affinity and selectivity for its target receptor.