331821-49-9

Basic information

• Product Name: N-Boc-L-2,2-dimethylthiazolidine-4-carbonyl-L-ethylglycyl-L-phenylalanyl-L-methionine methyl ester
• Synonyms: N-Boc-L-2,2-dimethylthiazolidine-4-carbonyl-L-ethylglycyl-L-phenylalanyl-L-methionine methyl ester
• CAS NO: 331821-49-9
• Molecular Weight: 638.85
• Mol File: 331821-49-9.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: N-Boc-L-2,2-dimethylthiazolidine-4-carbonyl-L-ethylglycyl-L-phenylalanyl-L-methionine methyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: N-Boc-L-2,2-dimethylthiazolidine-4-carbonyl-L-ethylglycyl-L-phenylalanyl-L-methionine methyl ester(331821-49-9)
• EPA Substance Registry System: N-Boc-L-2,2-dimethylthiazolidine-4-carbonyl-L-ethylglycyl-L-phenylalanyl-L-methionine methyl ester(331821-49-9)

Safety Data

• Hazardous Substances Data: 331821-49-9(Hazardous Substances Data)

Upstream product

• 331821-82-0 N-Boc-L-2,2-dimethylthiazolidine-4-carbonyl-L-ethylglycine methyl ester 
• 120711-54-8 L-(-)-N-(tert-butyloxycarbonyl)-2,2-dimethylthiazolidinecarboxylic acid pentafluorophenyl ester 
• 40290-63-9 Methyl ester of N-t-butyloxycarbonyl-L-phenylalanyl-L-methionine 

Relevant articles and documents

Cyclopropane-derived peptidomimetics, design, synthesis, and evaluation of novel Ras farnesyltransferase inhibitors

Trisubstituted cyclopropanes have previously been established as rigid replacements of dipeptide arrays in several biological systems. Toward further evaluating the utility of these dipeptide mimics in the design of novel CA1A2X-based inhibitors of Ras farnesyltransferase (FTase), the conformationally constrained, diastereomeric pseudopeptides CAbuψ[COcpCO]FM 7-9, the flexible analogue CAbuψ[CHOHCH2]FM (10), and the tetrapeptide CAbuFM (6) were prepared. The orientations of the two peptide backbone substituents and the phenyl group on the cyclopropane rings in 7-9 were specifically designed to probe selected topological features of the hydrophobic binding pocket of the A2 subsite of FTase. The syntheses of the requisite trisubstituted cyclopropane carboxylic acid 22 and the diastereomeric cyclopropyl lactones 32a,b featured diastereoselective intramolecular cyclopropanations of chiral allylic diazoacetates and a new method for introducing side chains onto the C-terminal amino acid of cyclopropane-derived dipeptide replacements via the opening of an N-Boc-aziridine with an organocuprate. These cyclopropane intermediates were then converted into the targeted FTase inhibitors 7-9 by standard peptide coupling techniques. The pseudopeptides 7-9 were found to be competitive inhibitors of Ras FTase with IC50s of 1055 nM for 7, 760 nM for 8, and 7200 nM for 9. The flexible analogue 10 of these constrained inhibitors exhibited a IC50 of 320 nM and hence was slightly more potent than 7 and 8. All of these pseudopeptides were less potent than the tetrapeptide parent CAbuFM (6), which had an IC50 of 38 nM. Because 7 and 8 are approximately equipotent, it appears that the orientation of the peptide backbone substituents on the cyclopropane rings in 7 and 8 do not have any significant effect on binding affinity and that multiple binding modes are possible without significant changes in affinity. On the other hand, this flexibility does not extend to the orientation of the side chain of the A2 residue as 7 and 8 were both nearly i order of magnitude more potent than 9. Comparison of the relative potencies of 6 and 10 suggests that the amide linkage between the A1 and the A2 residues of CA1A2X-derived FTase inhibitors is important.