Lactam-bridged dimers

Synthesis of a series of disulfide- (Leban et al., 1996) and lactam-bridged analogs of 66 afforded both the desired monomeric compounds along with the corresponding dimers (Figure 8b). Table 6 shows the ability of these compounds, compared to that of NPY and NPY analogs, to displace specifically bound pH] NPY from rat brain membranes and [l25I]NPY from SK-N-MC neuroblastoma cells. 

Conventional synthesis of lactam-bridged cyclic peptides have in the past utilized the efficient assembly of the linear sequence by SPPS and upon cleavage from the solid support, cyclization of the semi-protected peptide is then carried out in solution. This method requires a dilute medium to minimize dimerization as a result of intermolecular condensation of the linear sequences (81). As a consequence, the reaction rate and yield are drastically reduced. 

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