Peptides cyclic structures

The effect of C ,C -disubstituted amino acids (aaAAs) on peptide secondary structure has been studied in recent years.2a d While longer side-chain C ,C -di-n-alkyl amino acids promote extended peptide conformation,23 alicyclic aaAAs, in which the Ca carbon forms a cyclic bridge with itself, such a 1-aminocyclopentane-l-carboxylic acid (Ac5c) and 1-aminocyclohexane-l-carboxylic acid (Ac6c), have helix-forming characteristics similar to those of 1 -aminoisobutyric acid (Aib).2ax... 

Many peptide antibiotics have novel structural motifs, such as cyclic structures and are often further modified, (such as in jS-lactamic antibiotics) and conjugated with sugars, lipids, and other molecules. 

Cyclic structures can form as a result of side reactions. One of the most common examples is the formation of diketopiperazines during the coupling of the third amino acid onto the peptide chain (Fig. 7). Intramolecular amide bond formation gives rise to a cyclic dipeptide of a six-membered ring structure, causing losses to the sequence and regeneration of the hydroxyl sites on the resin. The nucleophilic group on the resin can lead to fiuther unwanted reactions [14]. 

Many medicinally useful peptides have cyclic structures. Cyclization may result if the amino acids at the two termini of a linear peptide link up to form another peptide bond. Alternatively, ring formation can very often be the resnlt of ester or amide linkages that utilize side-chain functionalities (CO2H, NH2, OH) in the constituent amino acids. 

Beta structures are found in many small peptides. Tire hormone oxytocin (Fig. 2-4), the antibiotics gramicidin S (Fig. 2-4) and valinomycin (Fig. 8-22), and the mushroom peptide antamanide (Box 28-B) are among these. The cyclic structures of these compounds favor formation of antiparallel (3 strands with sharp turns at the ends. Polypeptide antibiotics that have alternating... 

Peptides with a motif that favor a cyclic structure are recommended in this approach. Two peptides derived from the V3 loop of the surface protein gpl20 of human immunodeficiency virus, GPGRAFYTTKNIIG and KRKRIHIGPGRAFYTTKNIIG, are used to illustrate this example. Both peptides contain a turn motif, GPGR, in the middle of the sequence that may facilitate the ring-chain tautomerization in the cyclization process. 

---