A QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP STUDY OF SOME SUBSTANCE P-RELATED PEPTIDES - A MULTIVARIATE APPROACH USING PLS AND VARIABLE SELECTION

Nine new analogues of substance P (SP) were designed using quantitativ e sequence-activity models based on the amino acid z-scales with PLS a s the statistical method and the GOLPE procedure for variable selectio n. The nine SP analogues were synthesised by solid-phase peptide synth esis and tested for affinity to the NK-1 receptor from rat brain with radio receptor assay using [I-125]-Bolton-Hunter substance P as labell ed ligand. All of the new substance P analogues showed high affinities , with IC50 values of less than 0.8 nM. One analog, s-Arg-Ala-Lys-Phe- Met-Met-Phe-Phe-Gly-Leu-Let-NH2, showed a exceptional high affinity fo r the NK1 receptor, with IC50 = 5 pM. (C) Munksgaard 1997.