a chemical conjugate of peptidase-resistant [Sar⁹, Met(O₂)¹¹] analog of Substance P
and the ribosome-inactivating protein, saporin
targets cells expressing substance P (NK-1) receptor

SSP-SAP is a conjugation of saporin and SSP, the Sar⁹, Met(O₂)¹¹ analog of Substance P. These two amino acid replacements are at two sites of digestion by tissue proteases (there is a third that is still in the analog, so it does eventually get degraded). As such, the SSP-SAP conjugate is more resistant to proteases and so has a longer half-life than SP-SAP in tissue. Since the targeting agent is, of course, necessary for the cytotoxic activity, SSP-SAP will diffuse farther, and thus hit more target cells.

SSP-SAP is now also being used to replace SP-SAP (Cat. #IT-07). Scientific advisors have given counsel for this replacement because SSP-SAP is a superior lesioning agent in many situations, due to its targeting vehicle, a protease-resistant form of substance P. An excellent example is the paper by Martin and Sloviter, J Comp Neurol 436:127-152 (2001), in which after ineffective intraparenchymal injection of SP-SAP in the hippocampus, SSP-SAP was used with tremendous efficacy. In almost all applications we expect SSP-SAP will be used at a lower dose than SP-SAP.

Elimination of Specific Cell Type, In Vivo

• The conjugate is specific for substance P receptor-bearing neurons.
• All other cells are left untouched, even when they are the predominant cell type.
• This specific analog of Substance P-saporin resists peptidase digestion, allowing a greater diffusion from the injection site before its metabolism.
• Not suitable for retrograde transport.

Effective Tool to Study Behavior

• Behaviors associated with pain perception are greatly affected by the injection of SSP-SAP into the spinal cord of rats.