Cystine peptides, cyclic

P. J. Milburn, Y. Konishi, Y. C. Meinwald, and H. A. Scheraga, J. Am. Chem. Soc., 109, 4486 (1987). Erratum ibid., 109, 8123 (1987). Chain Reversals in Model Peptides Studies of Cystine-Containing Cyclic Peptides. I. Conformational Free Energies of Cyclization of Hexapeptides of Sequence Ac-Cys-X-Pro-Gly-Y-Cys-NHMe. 

Disulfides from thioethers Cyclic cystine peptides... 

The peptides discussed so far are defined by a common genetic pattern or architectural feature, such as their sequence or disulfide bond pattern. In this section we discuss peptides that share a common mode of action but may arise from different peptide families. Proteinase inhibitors (Pis) come in an astounding range of sizes, from the smallest gene-encoded cyclic peptide known to date, sunflower trypsin inhibitor 1 (SFTI-1), ° a 14-residue cyclic peptide with a single disulfide bond, to squash inhibitors that are approximately 30 residues in size and feature the cystine knot motif, to 53-residue Pis found in Nicotiana... 

Suggested preferred conformations can be fixed by cyclization. Cystine has been used to obtain cyclic analogues of Org 2766 viz. H-Cys-Glu-His-Cys-D-Lys-Phe-OH, H-Cys-Ala-Ala-Cys-D-Lys--Phe-OH and H-Cys-Ala-Ala-Phe-D-Lys-Cys-OH (patent application 0052028 of Roussel-UcIaf), and the peptides were tested for activity in the pole-jumping test. Unfortunately, one cannot conclude from their data if cyclization has resulted in an increase or decrease in activity since no reference peptide has been included to compare potencies. In the literature cyclization of [Lys ]ACTH--(5-10) (the COOH group of Gly with the 6-NH2 function of Lys ) has been reported the resulting peptide was inactive in steroidogenesis (61). Increase of the ring size with three atoms (a Gly residue), however, resulted in a peptide that was more active... 

J.P. Tam, Y.A. Lu, Synthesis of large cyclic cystine-knot peptide by orthogonal coupling strategy using unprotected peptide precursor, Tetrahedron Lett. 1997, 38, 5599. 

Ranganathan. D. Haridas, V. Karle. LL. Cystinophanse. a novel family of aromatic-bridged cystine cyclic peptides ... 

In the remaining part of the talk I should like to give some examples which illustrate the importance of having S-protected cysteines such as those mentioned above. First, they can be used for the preparation of not only simple peptides of cystine and cysteine but also of cyclic peptides of the oxytocin (31) or the vasopressin type. 

Despite these successes serious side reactions can result from the action of alkali on cysteine or cystine-containing peptides. Open-chain unsymmetrical cystine derivatives [92, 103, 166] and some cyclic molecules including oxytocin [153] and calcitonin [24, 25] are known to undergo rapid base-catalyzed disulphide interchange yielding symmetrical disulphides or mixtures of polymer and parallel and antiparallel dimers [107, 153]. Furthermore the possibility of /3-elimination of trityl, benzhydryl, and benzyl mercaptide ion from the corresponding peptide bound cysteine residue is known [154] the extent of... 

---