A frame shifted disulfide bridged analogue of angiotensin II

Design and synthesis of all diastereomers of cyclic pseudo-dipeptides as mimics of cyclic CXCR4 pentapeptide antagonists

“…RCM has been shown to be a useful method for synthesizing constrained peptides and forming 8-10-membered rings 20a,22 and 13-20membered ring cycles. 11,12,20b,c,d Nevertheless, the only reported example of RCM on an 11-membered, ring-constrained peptide failed, 11 but we expected that cyclization would be possible with a new generation of catalysts. Cyclization of these peptides was reported to be possible without protection of the amide bond to increase cis conformation for cycles of up to 10-membered rings.…”

“…9, 10 The use of constrained peptides or peptide mimics has become popular for increasing receptor affinity, for the development of new drugs, to investigate bioactive conformations, and to increase duration of action. On native peptides, constraints can be introduced by linkage between two points of the peptide (NH to NH, 11 NH to CO 2 H 12 or disulfide bridge 13 ) to fix a large secondary structure, generally a helix or sheets. The small secondary structures (turn, small helix, hairpin and E-or Z-amide bonds) can also be induced, stabilized or fixed by introduction in the sequence of one or several small constrained (Freidinger lactams 14 or azabicycloalkanes 15, 16 ), bulky (alkylprolines 17 ) or rigid (dipeptide isosteres 18,19 ) unnatural amino acids.…”