TABLE 2.

Cathepsin Stability of selected p1 substitutions compared to the reference peptide AcVRFFKNI.

Compound PV-	Sequence	Cathepsin/Cathepsin conc. (U/μmol compd)		pH	T1/2 (min) [Estimate]	Cleavage site (s)
004	Ac-VRFFKNI-NH2	B	0.30	5.5	4.6	Ac-VRF-//-FKNI-NH2
004	Ac-VRFFKNI-NH2	L	0.15	5.5	4.4	Ac-VRFF-//-KNI-NH2
004	Ac-VRFFKNI-NH2	S	0.30	5.5	21	Ac-VR-//-FF-//-K-//-NI-NH2
267	Ac-V-Chg-R-Tic-F-NH2	B	0.30	5.5	> 4 h [7 h]	Ac-V-Chg-R-Tic-F-//-NH2
267	Ac-V-Chg-R-Tic-F-NH2	S	0.30	5.5	> 4 h [7h]	Ac-V-Chg-R-Tic-F-//-NH2
267	Ac-V-Chg-R-Tic-F-NH2	S	0.15	5.5	20 h	ND
267	Ac-V-Chg-R-Tic-F-NH2	L	0.01	5.5	24 h	Ac-V-Chg//-R-Tic-F-NH2

Test compound and cathepsin solutions were prepared as described in Materials and Methods. Cathepsin enzymes at indicated concentrations were added to the compound solution and incubated for 4, 8, 16, 32, 64, 128, 256 min and 24 hr for analysis. Chg, cyclohexylglycine, Tic, tetrahydroisoquinolin-3-carboxylic acid, ND, no cleavage detected, all are tested as C-terminal amides.