Arginine rich peptides raised increased interest during the last years as they have the capability to cross cell and blood brain barrier membranes. However, synthesis of such peptides with standard Fmoc/tBu protocols is rather laborious. One option to avoid these difficulties is using ornithine at the respective position in the sequence and transfer it into arginine by appropriate guanylating reagents.

A number of different ornithine building blocks is available, all bearing orthogonal protecting groups to Fmoc/tBu standard protocols:

For guanylation in some cases normal guanidinopyrazole can be used. However, much better results are being achieved with the more reactive Bis-Boc and Bis-Z derivatives: