Practical synthesis of cyclic peptides, with an example of dependence of cyclization yield upon linear sequence

Cyclosporines: Biosynthesis and Beyond

“…The small side chains of the N-and C-terminal alanine residues of CsA also facilitate cyclization by allowing the ends to come close together into a suitable orientation for condensation. The d-configuration of the C-terminal alanine facilitates ring formation over side reactions as has been shown with other examples in the literature [77]. This is coincident with the strict selectivity of the A-domain of the last module incorporating for an l-amino acid and the strict d-epimer selectivity of the first A-domain module incorporating d-Ala 8 [48].…”

Macrocyclization Reactions: The Importance of Conformational, Configurational, and Template-Induced Preorganization

“…331,332 On the contrary, sequences with basic and polar residues next to the N-terminal residue (Nterminal Thr and an Arg-His-Ser motif) have been shown to be difficult to cyclize. 333 The combinatorial analysis carried out by Pei and co-workers revealed that peptides that are difficult to cyclize are generally rich in Lys(Boc) and Arg(Pbf) residues.…”

What are the structures of phakellistatin 2 and phakellistatin 4?

“…The yields strongly depend on the cyclization site [27]. We observed that head-to-tail cyclization of all-L-peptides gives the highest yield when cyclization in the i + 2 and i+ 3 position of a ~-turn in the final cyclic structure is chosen [15].…”